Bacterial atp synthase binding domain

ABSTRACT

This invention provides an isolated mutant atpE protein and departing from said mutant atpE protein the identification of an ATPase binding domain. This invention also provides related nucleic acids, vectors, host cells, pharmaceutical compositions and articles of manufacture. This invention further provides methods for determining whether a test compound interacts with an atpE protein, i.e. with the ATPase binding domain of the present invention, as well as pharmaceuticals compositions comprising said test compound, in particular as antimicrobials, more particular as antimycobacterial agent, even more particular for treating tuberculosis in a subject.

This invention provides an isolated mutant atpE protein and departingfrom said mutant atpE protein the identification of an ATPase bindingdomain. This invention also provides related nucleic acids, vectors,host cells, pharmaceutical compositions and articles of manufacture.This invention further provides methods for determining whether a testcompound interacts with an atpE protein, i.e. with the ATPase bindingdomain of the present invention, as well as pharmaceuticals compositionscomprising said test compound, in particular as antimicrobials, moreparticular as antimycobacterial agent, even more particular for treatingtuberculosis in a subject.

BACKGROUND OF THE INVENTION

After AIDS, tuberculosis (TB) is the leading cause of adult mortality(2-3 million deaths per year) in the world and is a critical impedimentto alleviating global poverty and suffering (1). Factors contributing tothe resurgence of the disease include difficulties in implementinganti-TB programs in many countries, the dramatic increase in the numberof immunosuppressed individuals—due mainly to HIV infection—and themovement of people through and from areas where TB is endemic. The TBand HIV epidemics fuel one another in co-infected people—currently 11million adults—increasing both morbidity and mortality (2, 3). Inaddition, TB is the leading cause of death in HIV-infected people (4).

Although first-line anti-TB drug regimens can achieve more than 90%efficacy rates, their complexity can lead to poor compliance whenadequate medical support and TB treatment programs are not availableand, in turn, to the emergence of resistance (5). Multidrug-resistant(MDR) strains of TB complicate treatment substantially (6). The GlobalAlliance for TB Drug Development has recommended that any new treatmentshould offer at least one of the following three advantages overexisting therapies: shortening or simplifying effective treatment of TB;increasing efficacy against MDR-TB; and improving treatment of thelatent form of TB infection. Such a new drug would greatly improvepatient compliance, thereby reducing the cost of TB treatment programslike the World Health Organization (WHO)'s Directly Observed TreatmentShort-course (DOTs) strategy (7).

Newer anti-TB candidates currently in preclinical and clinicaldevelopment tend to be either from existing families of drugs (such asmoxifloxacin), or analogs of first-line drugs such as MJH-98-1-81 (fromisoniazid), the oxazolidinones, and rifapentine (a close analog ofrifampin) (8). Although these new drugs may be potent, analog compoundsprovide only temporary solutions to resistance (9), as they rely on thesame mechanism of action as the existing families of drugs.

Antibiotics in general usually inhibit bacterial replication byinhibiting bacterial metabolism though a specific mechanism. Forexample, isoniazid interferes with the enzymatic machinery thatsynthesizes mycolic acids, necessary components of the cell wall, whilerifampicin interferes with the bacterial machinery for transcribing RNAfrom DNA. It is accordingly of interest to explore novel methods toidentify anti-TB compounds that target different mycobacterial specificaspects of cell growth and replication compared to the known agents.

SUMMARY OF THE INVENTION

This invention provides for isolated mutant atpE proteins, in particularencoded by the amino acid sequences selected from (SEQ ID No.1), (SEQ IDNo.2), (SEQ ID No.3), (SEQ ID No.4) and (SEQ ID No.5), an isolatednucleic acid encoding said mutant atpE proteins, in particular selectedfrom the group consisting of (SEQ ID No.6), (SEQ ID No.7), (SEQ IDNo.8), (SEQ ID No.9) and (SEQ ID No.10) and a vector comprising theinstant nucleic acid. In a particular embodiment the mutant atpE proteinis encoded by SEQ ID No.2 and the isolated nucleic acid sequenceencoding said protein consists of SEQ ID No.7.

This invention further provides a host-vector system comprising a hostcell having therein the instant expression vector.

This invention further provides an isolated cell comprising a mutantatpE protein, wherein said protein induces anti-microbial resistance inthe cell.

This invention further provides a method for identifying ananti-microbial compound said method comprising the steps of

(a) contacting a cell expressing an atpE protein with a test compoundunder physiological conditions;(b) determining whether the test compound interacts with the atpEprotein.

This invention further provides a method for evaluating the potential ofa test compound to interact with an atpE protein said method comprising;

(a) using molecular modeling techniques to generate a three-dimensionalstructure of the atpE protein;(b) employing computational means to perform a fitting operation betweenthe test compound and the three-dimensional structure of the atpEprotein; and(c) analyzing the results of said fitting operation to quantify theassociation of the test compound with the three dimensional structure ofthe atpE protein.

It is also an object of the present invention to provide a binding siteof an F₀ part of an ATPase comprising at least the amino acids Ala²⁴,Gly²⁷, Phe⁵³, Val⁵⁷, Gly⁵⁸, Glu⁶¹, Tyr⁶⁴ and Phe⁶⁵ of one C subunit; theamino acids Ser¹⁸², Leu¹⁸³, Ser¹⁸⁴, Leu¹⁸⁵, and Arg¹⁸⁶ of one A subunitand said amino acids having the atomic coordinates of any of Tables 3, 4or 5.

In a further object, the present invention provides the use of theaforementioned binding domain in a method to identify compounds thatinteract with the F₀ part of an ATPase and to their potential asanti-microbial compounds, in particular in a method to identifyanti-mycobacterial compounds.

It is accordingly, an object of the present invention to provide amethod of treating a subject with a microbially-based infection,comprising administering to the subject a compound that interacts withthe F₀ part of an ATPase, in particular with an atpE protein at theresistance-conferring mutation sites or with the binding site of thepresent invention. This invention further provides a method for treatinga subject afflicted with tuberculosis comprising administering to thesubject an agent that interacts with an atpE protein using any of theaforementioned screening methods. In the methods of treatment comprisingthe use of a compound that interacts with the F₀ part of an ATPase, inparticular with an atpE protein, compounds previously known to interactwith the F₀ part of an ATPase, and in particular with an atpE proteinare to be excluded. More in particular the use of the DARQ J compoundsdescribed in (11) in any of the disclosed method of treatments is to beexcluded.

This invention further provides for a pharmaceutical compositioncomprising an agent that interacts with an atpE protein in a cell, and apharmaceutically acceptable carrier. Finally, this invention providesfor an article of manufacture comprising a packaging and apharmaceutical agent, wherein (a) the pharmaceutical agent interactswith an atpE protein in a cell, and (b) the packaging comprises a labelindicating the use of the agent for treating a bacterial infection in asubject. In a particular embodiment the present invention provides theuse of DARQ J in the manufacture of an anti-microbial medicine.

This and further aspects of the present invention will be discussed inmore detail hereinafter.

BRIEF DESCRIPTION OF THE DRAWING

Table. 1 The minimum inhibitory concentrations (MICs) of the lead DARQcompound (J), that inhibited 90% of the growth of differentmycobacterial species. the number of strains tested were n=1, unlessotherwise indicated.

Table. 2 The amino acids surrounding the binding site for the DARQ Jcompound.

Table. 3 The atomic coordinates for the amino acids surrounding thebinding site for the DARQ J compound derived from both the wild type andDARQ J mutant M. tuberculosis strain.

Table 4. The atomic coordinates for the binding site for the DARQ Jcompound in the wild type M. tuberculosis.

Table 5. The atomic coordinates for the binding site for the DARQ Jcompound in the DARQ J mutant M. tuberculosis strain.

Table 6. The atomic coordinates for the mutant atpE protein (SEQ ID No.2) of M. tuberculosis.

Table 7. The atomic coordinates for the wild type atpE protein (SEQ IDNo. 1) of M. tuberculosis.

FIG. 1 Absolute configuration of R207910, hereinafter also referred toas J or DARQ J.

FIG. 2 atpE protein sequence alignments for M. tuberculosis and M.smegmatis mutants. Mtb_S: drug-sensitive strain of M. tuberculosisH37Rv, atpE (1-81). Accession number: Swiss-Prot Q10598 (SEQ ID No. 1).Mtb_R: drug-resistant strain of M. tuberculosis BK12, atpE (1-81) (SEQID No.2). Msm_S: drug-sensitive strain of M. smegmatis, atpE (1-86).Sequence obtained by the Institute for Genome Research (SEQ ID No.3).Msm_R09 (SEQ ID No.4) and R10 (SEQ ID No.5): drug-resistant strains ofM. smegmatis atpE (1-86). Sequences obtained in-house. Human: Homosapiens, ATP5G3 (66142). Accession number: Ensembl ENSP00000284727. Topnumbering: M. tuberculosis and M. smegmatis atpE. Bottom numbering: Hsapiens ATP5G3 (66-142) Shading indicates amino acid similarity usingBLOSUM62 matrix (black=high, grey=medium). Arrows indicate the positionsof the point mutations observed in the resistant strains.

FIG. 3 Total cellular ATP-measurement of M. tuberculosis in presence ofDARQ J, Isoniazid & DCCD. Relative Luminescence Units of Oxyluciferinmeasured at 526 nm, both in wild type M. tuberculosis and DARQ J mutantM. tuberculosis.

FIG. 4. Ribbon representation of the three C-subunits (A Chain, K Chainand L Chain) and the A subunit (M chain) which form together the bindingsite for the DARQ J compound.

DETAILED DESCRIPTION Definitions

As used in this application, except as otherwise expressly providedherein, each of the following terms shall have the meaning set forthbelow.

“atpE protein” shall mean the C chain of the F0 subunit of ATPasecomplex as represented by SwissProt entry Q10598 for M. tuberculosis, ora protein having at least 70, 80, 90, 95, 97 or 99% sequence identity tosaid M. tuberculosis sequence.

“F₁F₀ ATPase” also referred to as ATPase, ATP synthase or F₀F₁ ATP aseshall mean a large-multisubunit complex that catalyses the synthesis orhydrolysis of ATP. F₀F₁ ATPases are composed of two domains: an F₁ part,which is extrinsic to the membrane and contains the catalytic sites andan F₀ part which spans the bilayer and contains a proton pore. The ATPases are found in the plasma membrane of bacteria, the thylakoidmembrane of chloroplasts, and the inner membrane of mitochondria wherethey use the energy of a proton electrochemical gradient to drive ATPsynthesis.

“Administering” shall mean delivering in a manner, which is effected orperformed using any of the various methods and delivery systems known tothose skilled in the art. Administering can be performed, for example,topically, intravenously, pericardially, orally, via implant,transmucosally, transdermally, intramuscularly, subcutaneously,intraperitoneally, intrathecally, intralymphatically, intralesionally,or epidurally. Administering can also be performed, for example, once, aplurality of times, and/or over one or more extended periods.

“Host cells” include, but are not limited to, bacterial cells, yeastcells, fungal cells, insect cells, and mammalian cells. Bacterial cellscan be transfected by methods well-known in the art such as calciumphosphate precipitation, electroporation and microinjection.

“Isolated”, with respect to atpE protein, shall mean an atpEprotein-containing membrane fragment preparation or other suitablepreparation wherein atpE retains its natural function and is free fromsome or all of the other proteins in its native milieu. It is meant toinclude membrane preparations comprising the F₀ part of an F₀F₁ ATPase,in particular an F₀ part comprising the mutant atpE proteins of thepresent invention.

“Bacterial cell” shall mean any bacterial cell. Bacterial cells include,without limitation, cells which are normal, abnormal and transformed,and are exemplified by mycobacteria, in particular Mycobacteriumtuberculosis and Mycobacterium smegmatis, corynebacteria, nocardia,gram-positive bacteria such as for example streptococcus, staphylococcusand enterococcus or gram negative bacteria such as for exampleEscherichia coli, Heamophilus influenzae and Helicobacter pylori.

The terms “nucleic acid” and “polynucleotide” are used interchangeablyherein, and each refers to a polymer of deoxyribonucleotides and/orribonucleotides. The deoxyribonucleotides and ribonucleotides can benaturally occurring or synthetic analogues thereof.

The term “physiological conditions” shall mean, with respect to a givencell, such conditions, which would normally constitute the cell'sbiochemical milieu. The cell's biochemical milieu includes, withoutlimitation some or all the proteases to which the cell is normallyexposed. Such conditions include, but are not limited, to in vivoconditions.

The terms “polypeptide,” “peptide” and “protein” are usedinterchangeably herein, and each means a polymer of amino acid residues.The amino acid residues can be naturally occurring or chemical analoguesthereof. Polypeptides, peptides and proteins can also includemodifications such as glycosylation, lipid attachment, sulfation,hydroxylation, and ADP-ribosylation.

“Subject” shall mean any animal, such as a mammal or a bird, including,without limitation, a cow, a horse, a sheep, a pig, a dog, a cat, arodent such as a mouse or rat, a turkey, a chicken and a primate. In thepreferred embodiment, the subject is a human being.

“Treating” shall include, without limitation, eliminating, reversing thecourse of, slowing the progression of, reducing the symptoms of, orotherwise ameliorating, a disease in a subject.

“Vector” shall mean any nucleic acid vector known in the art. Suchvectors include, but are not limited to, plasmid vectors, cosmidvectors, and bacteriophage vectors.

The terms “Candidate substance” and “Test compound” are usedinterchangeably and refer to a substance that is believed to interactwith another moiety, i.e. the atpE protein, as a biological responsemodifier. For example a representative candidate substance is believedto interact with an atpE protein and is believed to modify the ATPaseactivity. Exemplary candidate substances that can be investigated usingthe methods of the present invention include, but are not restricted topeptides, enzymes, enzyme substrates, co-factors, sugars,oligonucleotides, chemical compounds small molecules and monoclonalantibodies.

“Modulate” shall mean an increase, decrease or other alteration of anyor all chemical and biological activities or properties of a wild typeor mutant atpE protein.

“Interact” shall mean detectable interactions between molecules,including “binding” interactions between molecules. Interactions can,for example, be protein-protein or protein-nucleic acid in nature. Suchinteractions can be detected using art know procedures, for example,yeast two-hybrid assay, immunoprecipitation, SPA-assay or filter bindingassays.

As used herein, the term “atomic coordinates” or “structure coordinates”refers to mathematical coordinates that describe the positions of atomsin Protein Data Bank (PDB) format, including X, Y, Z and B for eachatom. Those of skilled in the art understand that a set of structurecoordinates determined by X-ray crystallography is not without standarderror. For the purpose of this invention, any set of structurecoordinates for ATPsynthase from any source having a root mean squaredeviation of non-hydrogen atoms of less than 1.5 Å when superimposed onthe non-hydrogen atom position of the corresponding atomic coordinatesof Tables 3, 4, 5, 6 or 7 are considered substantially identical orhomologous. In a more preferred embodiment, any set of structurecoordinates for ATPsynthase from any source having a foot mean squaredeviation of non-hydrogen atoms of less than 0.75 Å when superimposed onthe non-hydrogen atom position of the corresponding atomic coordinatesof Tables 3, 4, 5, 6 or 7 are considered substantially identical.

Embodiments of the Invention

Mutant atpE Proteins

This invention provides for isolated mutant atpE proteins, in particularbacterial atpE proteins, more particular mycobacterial atpE proteins,even more particular M. tuberculosis or M. smegmatis atpE proteins. Themutation is selected from single point mutations, insertions ordeletions. In one embodiment of the invention the mutation consist of atleast one point mutation located in any one of amino acids 20 to 40, inparticular 30 to 40, preferable in amino acid 34 or of amino acids 60 to75, in particular 62 to 73, preferably in amino acid 69 as shown in thesequence alignment of FIG. 2. In a further embodiment the isolatedmutant atpE proteins are selected from Mtb_R (SEQ ID No.2), Msm_R09 (SEQID No.4) and Msm_R10 (SEQ ID No.5) as shown in FIG. 2 or of an aminoacid sequence having at least 70, 80, 90, 95, 97 or 98% sequenceidentity to any of the aforementioned amino acid sequences.

This invention further provides an isolated nucleic acid encoding saidmutant atpE proteins. In one embodiment said nucleic acid sequenceconsists of all genes that encode an F₀ part, such as for exampledescribed in J. Biol. Chem., 1994, Vol. 269(10), p. 7285-7289, whereinsaid genes are transcribed from a single promoter and comprise thenucleic acid sequence encoding the mutant atpE protein of the presentinvention. The nucleic acid can be DNA or RNA, and preferably DNA andare in a further embodiment selected from the nucleic acid sequencesencoding Mtb_R (SEQ ID No.7) Msm_R09 (SEQ ID No.9), Msm_R10 (SEQ IDNo.10) or a nucleic acid sequence having at least 70, 80, 90, 95, 97 or98% sequence identity to any of the aforementioned nucleic acidsequences.

The percentage identity of nucleic acid and polypeptide sequences can becalculated using commercially available algorithms which compare areference sequence with a query sequence. The following programs(provided by the National Center for Biotechnology Information) may beused to determine homologies/identities: BLAST, gapped BLAST, BLASTN andPSI-BLAST, which may be used with default parameters.

The algorithm GAP (Genetics Computer Group, Madison, Wis.) uses theNeedleman and Wunsch algorithm to align two complete sequences thatmaximizes the number of matches and minimizes the number of gaps.Generally, the default parameters are used, with a gap creationpenalty=12 and gap extension penalty=4.

Another method for determining the best overall match between a nucleicacid sequence or a portion thereof, and a query sequence is the use ofthe FASTDB computer program based on the algorithm of Brutlag et al(Comp. App. Biosci., 6; 237-245 (1990)). The program provides a globalsequence alignment. The result of said global sequence alignment is inpercent identity. Suitable parameters used in a FASTDB search of a DNAsequence to calculate percent identity are: Matrix=Unitary, k-tuple=4,Mismatch penalty=1, Joining Penalty=30, Randomization Group Length=0,Cutoff Score=1, Gap Penalty=5, Gap Size Penalty=0.05, and WindowSize=500 or query sequence length in nucleotide bases, whichever isshorter. Suitable parameters to calculate percent identity andsimilarity of an amino acid alignment are: Matrix=PAM 150, k-tuple=2,Mismatch Penalty=1, Joining Penalty=20, Randomization Group Length=0,Cutoff Score=1, Gap Penalty=5, Gap Size Penalty=0.05, and WindowSize=500 or query sequence length in nucleotide bases, whichever isshorter.

This invention further provides a vector comprising the instant nucleicacid. In one embodiment the vector is a plasmid vector.

This invention further provides a host-vector system comprising a hostcell having therein the instant plasmid vector. The cell can beprokaryotic or eukaryotic, in one embodiment the host cell is abacterial cell, in particular a mycobacterial cell such as for exampleM. tuberculosis or M. smegmatis.

This invention further provides an isolated cell comprising a mutantatpE protein, which protein induces anti-microbial resistance in thecell. In one embodiment the isolated cell consists of a M. smegmatiscell transformed with a mutant mycobacterial atpE protein, in particulartransformed with a mutant mycobacterial atpE protein wherein themutation consist of at least one point mutation located in any one ofamino acids 20 to 40, in particular 30 to 40, preferable in amino acid34 or of amino acids 60 to 75, in particular 62 to 73, preferably inamino acid 69 as shown in the sequence alignment of FIG. 2.

Screening Methods

This invention further provides a method for identifying ananti-microbial compound said method comprising the steps of

(a) contacting a cell expressing an atpE protein with a test compoundunder physiological conditions;(b) determining whether the test compound interacts with the atpEprotein.

In one embodiment the atpE protein used in the aforementioned method,consist of a bacterial atpE protein, in particular a mycobacterialprotein and is meant to include both the wild type atpE proteins as wellas the mutant atpE proteins as described hereinbefore. In a furtherembodiment of the present invention, the mycobacterial atpE protein usedin the aforementioned method consists of a mutant mycobacterial atpeprotein according to the invention. In a particular embodiment of theaforemeantioned assay a host cell transformed with a mutant atpE proteinof the invention is used and the interaction of the test compound withsaid atpE protein is assessed by determining the possible inhibition ofthe enzymatic activity of the F₁Fo-ATPase comprising said mutant atpEprotein. Inhibition of the F₁Fo-ATPase activity is determined using artknown procedures, such as for example by adding the substance to asystem comprising the F₁Fo-ATPase and ATP as a substrate, with detectionof the enzymatic activity by coupling the production of ADP to theoxidation of NADH via pyruvate kinase and lactate hydrogenase reactions.

In one embodiment of the assay, the atpE protein may be employed in abinding assay. Binding assays may be competitive or non-competitive.Such an assay can accommodate the rapid screening of a large number ofcompounds to determine which compounds, if any, are capable of bindingto the polypeptides.

-   -   Within this context, the present invention provides a method to        identify whether a test compound binds to an isolated atpE        protein of the present invention, and is thus a potential        anti-microbial compound, said method comprising;    -   a) contacting cells expressing the atpE protein wherein such        cells do not normally express said atpE protein, with the test        compound in the presence and absence of a compound known to bind        the atpE protein,    -   b) determine the binding of the test compound to the atpE        protein using the compound known to bind to the atpE protein as        a reference.

Binding of the test compound or of the compound known to bind to theatpE protein, hereinafter also referred to as reference compound, isassessed using art-known methods for the study of protein-ligandinteractions. For example, such binding can be measured by employing alabeled substance or reference compound. The test compound or referencecompound, in particular compound J (FIG. 1) can be labeled in anyconvenient manner known in the art, e.g. radioactively, fluorescently orenzymatically. In a particular embodiment of the aforementioned method,the compound known to bind to the atpE protein, also known as thereference compound is detectably labeled, and. Said label is used todetermine the binding of the test compound to the atpE protein. Saidreference compound being labeled using a radiolabel, a fluorescent labelor an enzymatic label, more preferably a radiolabel.

In an alternative embodiment of the present invention, theaforementioned binding assays are performed on a cellular composition,i.e a cellular extract, a cell fraction or cell organels comprising anatpE protein as defined hereinbefore. More in particular, theaforementioned binding assays are performed on a cellular composition,i.e. a membrane preparation comprising an atpE protein as definedhereinbefore, wherein said cellular composition, i.e. membranepreparation is obtained from a M. smegmatis cell transformed with amutant mycobacterial atpE protein, in particular transformed with amutant mycobacterial atpE protein wherein the mutation consist of atleast one point mutation located in any one of amino acids 20 to 40, inparticular 30 to 40, preferable in amino acid 34 or of amino acids 60 to75, in particular 62 to 73, preferably in amino acid 69 as shown in thesequence alignment of FIG. 2. Taking the numbering of Mtb_S (SEQ IDNo.1) or of Mtb_R (SEQ ID No.2) as a reference, the aforementionedregions correspond to amino acids 14 to 34, in particular 24 to 34,preferably in amino acid 28 or to amino acids 54 to 69, in particular 56to 67, preferably to amino acid 63.

In one embodiment the binding assays are performed using membranepreparations. These membrane preparations can be used in conventionalfilter-binding assays (eg. Using Brandel filter assay equipment) or inhigh throughput Scintillation Proximity type binding assays (SPA andCylostar-T flashplate technology; Amersham Pharmacia Biotech) to detectbinding of radio-labelled atpE ligands (including ³H labelled DARQs) anddisplacement of such radio-ligands by competitors for the binding site.Radioactivity can be measured with Packard Topcount, or similarinstrumentation, capable of making rapid measurements from 96-, 384-,1536-microtitre well formats. SPA/Cytostar-T technology is particularlyamenable to high throughput screening and therefore this technology issuitable to use as a screen for compounds able to displace standardligands.

Another approach to study binding of ligands to atpE protein in anenvironment approximating the native situation makes use of a surfaceplasmon resonance effect exploited by the Biacore instrument (Biacore).atpE protein in membrane preparations or whole cells could be attachedto the biosensor chip of a Biacore and binding of ligands examined inthe presence and absence of compounds to identify competitors of thebinding site.

Molecular Modeling

This invention further provides a method for evaluating the potential ofa test compound to interact with an atpE protein said method comprising;

(a) using molecular modeling techniques to formulate a three dimensionalstructure of the atpE protein;(b) employing computational means to perform a fitting operation betweenthe test compound and the three-dimensional structure of the atpEprotein; and(c) analyzing the results of said fitting operation to quantify theassociation of the test compound with the three dimensional structure ofthe atpE protein.

Molecular modeling techniques are known in the art, including bothhardware and software appropriate for creating and utilizing models ofreceptors and enzyme conformations.

Numerous computer programs are available and suitable for the processesof computer modeling, model building and computationally identifying,selecting and evaluating potential atpE interacting compounds in themethods described herein. These include for example, GRID (availablefrom Oxford University, UK), MCSS (available from Accelrys, Inc., SanDiego, Calif.), AUTODOCK (available from Oxford Molecular Group), FLEX X(available form Tripos, St. Louis. MO), DOCK (available from Universityof California, San Francisco, Calif.), CAVEAT (available from Universityof California, Berkeley), HOOK (available from Accelrys, Inc., SanDiego, Calif.) and 3D database systems such as MACCS-3D (available fromMDL Information Systems, San Leandro, Calif.), UNITY (available fromTripos, St. Louis. MO) and CATALYST (available from Accelrys, Inc., SanDiego, Calif.). Potential candidate substances may also becomputationally designed “de novo’ using software packages as LUDI(available from Biosym Technologies, San Diego, Calif.), LEGEND(available from Accelrys, Inc, San Diego, Calif.) and LEAPFROG(available from Tripos, St. Louis. MO). Compound deformation energy andelectrostatic repulsion, may be analysed using programs such as GAUSSIAN92, AMBER, QUANTA/CHARMM and INSIGHT II/DISCOVER. These computerevaluation and modeling techniques may be performed on any suitablehardware including for example, workstations available from SiliconGraphics, Sun Microsystems and others. These modeling techniques,methods, hardware and software packages are representative and are notintended to be a comprehensive listing. Other modeling techniques knownin the art may also be employed in accordance with this invention. Seefor example, N. C. Cohen, Molecular Modeling in Drug Design, AcademicPress (1996).

In one embodiment of the present invention, the three-dimensionalstructure of the atpE protein is generated using the atomic coordinatesof the Ile28, Glu61 and Ule63 of E. coli (Protein Database 1Q01) +/− aroot mean square deviation of the backbone atoms of said amino acids ofnot more that 10 Å, preferably not more that 5 Å.

As provided in the examples hereinafter, it has been an object of thepresent invention to provide the three-dimensional structure of the atpEprotein. Tables 6 and 7 provide the atomic coordinates for the mutantand wild type atpE protein with SEQ ID No.2 and SEQ ID No.1. Thus, inone embodiment the three-dimensional structure of the atpE protein isgenerated using the atomic coordinates of Tables 6 or 7. In a particularembodiment the three-dimensional structure of the atpE protein isgenerated using the atomic coordinates of Table 7. The DARQ J compoundinhibits the interaction of Arg¹⁸⁶ of the A subunit with Glu⁶¹ of theC-subunit in its deprotonated from. It is accordingly an object of thepresent invention to provide the use of the atomic coordinates of Tables6 or 7 in a method to evaluate the potential of a test compound tointeract with an atpE protein.

Binding Site

In another embodiment the present invention provides thecharacterization of a binding site in the F₀ part of an ATPase. Thisbinding site, identified as being capable of binding the DARQ Jcompound, was found to coincide with the regions identifiedhereinbefore, as the resistance-conferring mutation sites in the atpEproteins of M. tuberculosis and M. smegmatis (17). Hence, the presentinvention provides a binding site in the F₀ part of an ATPasecharacterised in that it comprises the resistance-conferring mutationsites of an atpE protein. The resistance-conferring mutation sites asused herein refer to amino acids 14 to 34, in particular 24 to 34 and toamino acids 53 to 69, in particular 56 to 67 of an atpE protein, takingthe numbering of Mtb_S (SEQ ID No.1) or of Mtb_R (SEQ ID No.2) as areference.

In a further embodiment the binding site comprises at least the aminoacids Ala²⁴, Gly²⁷, Phe⁵³, Val⁵⁷, Gly⁵⁸, Glu⁶¹, Tyr⁶⁴ and Phe⁶⁵ of one Csubunit and the amino acids Ser¹⁸², Leu¹⁸³, Leu¹⁸⁵, and Arg¹⁸⁶ of one Asubunit (having for the A subunit, the codes Ser 206-Leu 207-Leu 209 andArg 210 in Tables 3, 4 and 5), wherein said amino acids have the atomiccoordinates of any of Tables 3, 4 or 5 or homologous structurecoordinates comprising a root mean square deviation of non-hydrogenatoms of less than about 1.5 Å, preferably not more that 0.75 Å, whensuperimposed on the non-hydrogen atom positions of the correspondingatomic coordinates of Tables 3, 4 or 5. In a particular embodiment thebinding site comprises amino acids Ala²¹, Gly²⁵ of a first C subunit;amino acids Ala²⁴, Gly²⁷, Phe⁵³, Phe⁵⁴, Val⁵⁷, Gly⁵⁸, Glu⁶¹, Tyr⁶⁴,Phe⁶⁵ of a second C subunit; amino acids Met¹⁷, Gly¹⁹, Gly²⁰, Ala²¹,Ile²², Gly²³, Ala²⁴, Gly²⁵, Ile²⁶, Gly²⁷, Asp²⁸, Gly²⁹, Ala³¹, Phe⁵³,Thr⁵⁶, Val⁵⁷, Gly⁵⁸, Leu⁵⁹, Val⁶⁰, Glu⁶¹, Ala⁶², Ala⁶³/Pro⁶³, Tyr⁶⁴,Phe⁶⁵ of a third C subunit and amino acids Leu¹⁸³, Leu¹⁸⁵ and Arg¹⁸⁶ ofan A subunit; wherein said amino acids have the atomic coordinates ofany of Tables 3, 4 or 5 or homologous structure coordinates comprising aroot mean square deviation of non-hydrogen atoms of less than about 1.5Å, preferably not more that 0.75 Å, when superimposed on thenon-hydrogen atom positions of the corresponding atomic coordinates ofTables 3, 4 or 5. In an even more particular embodiment the binding siteconsists of the amino acids Ala²¹, Gly²⁵ of a first C subunit; aminoacids Ala²⁴, Gly²⁷, Phe⁵³, Phe⁵⁴, Val⁵⁷, Gly⁵⁸, Glu⁶¹, Tyr⁶⁴, Phe⁶⁵ of asecond C subunit; amino acids Met¹⁷, Gly¹⁹, Gly²⁰, Ala²¹, Ile²², Gly²³,Ala²⁴, Gly²⁵, Ile²⁶, Gly²⁷, Asp²⁸, Gly²⁹, Ala³¹, Phe⁵³, Thr⁵⁶, Val⁵⁷,Gly⁵⁸, Leu⁵⁹, Val⁶⁰, Glu⁶¹, Ala⁶², Ala⁶³/Pro⁶³, Tyr⁶⁴, Phe⁶⁵ of a thirdC subunit and amino acids Leu¹⁸³, Leu¹⁸⁵, and Arg¹⁸⁶ of an A subunit;wherein said amino acids have the atomic coordinates of any of Tables 3,4 or 5. In a most particular embodiment the binding site consists of theamino acids Ala²¹, Gly²⁵ of a first C subunit; amino acids Ala²⁴, Gly²⁷,Phe⁵³, Phe⁵⁴, Val⁵⁷, Gly⁵⁸, Glu⁶¹, Tyr⁶⁴, Phe⁶⁵ of a second C subunit;amino acids Met¹⁷, Gly¹⁹, Gly²⁰, Ala²¹, Ile²², Gly²³, Ala²⁴, Gly²⁵,Ile²⁶, Gly²⁷, Asp²⁸, Gly²⁹, Ala³¹, Phe⁵³, Thr⁵⁶, Val⁵⁷, Gly⁵⁸, Leu⁵⁹,Val⁶⁰, Glu⁶¹, Ala⁶², Ala⁶³/Pro⁶³, Tyr⁶⁴, Phe⁶⁵ of a third C subunit andamino acids Leu¹⁸³, Leu¹⁸⁵ and Arg¹⁸⁶ of an A subunit; wherein saidamino acids have the atomic coordinates of Table 3.

It is accordingly an object of the present invention to evaluate thepotential of a test compound to interact with an atpE protein using theatomic coordinates as outlined above, in computational screeningprograms. In one embodiment, the present invention provides a method toevaluate the potential of a test compound to interact with an atpEprotein, said method comprising;—molecular modeling techniques togenerate the three-dimensional structure of a binding site of an F₀ partof an ATPase;—employing computational means to perform a fittingoperation between the test compound and the three-dimensional structureof the binding site; and —analyzing the results of said fittingoperation to quantify the association of the test compound with thethree-dimensional structure of the binding site. In an furtherembodiment of the present invention, the three-dimensional structure ofthe binding site is generated using the atomic coordinates of Tables 3,4 or 5 or homologous structure coordinates comprising a root mean squaredeviation of non-hydrogen atoms of less than about 1.5 Å, preferably notmore that 0.75 Å, when superimposed on the non-hydrogen atom positionsof the corresponding atomic coordinates of Tables 3, 4 or 5. In aparticular embodiment the three-dimensional structure is generated usingthe atomic coordinates of the amino acids Ala²¹, Gly²⁵ of the A Chain ofany of Tables 3, 4 or 5; the amino acids Ala²⁴, Gly²⁷, Phe⁵³, Phe⁵⁴,Val⁵⁷, Gly¹⁸, Glu⁶¹, Tyr⁶⁴, Phe⁶⁵ of the K Chain of any of Tables 3, 4or 5; the amino acids Met¹⁷, Gly¹⁹, Gly²⁰, Ala²¹, Ile²², Gly²³, Ala²⁴,Gly²⁵, Ile²⁶, Gly²⁷, Asp²⁸, Gly²⁹, Ala³¹, Phe⁵³, Thr⁵⁶, Val⁵⁷, Gly⁵⁸,Leu⁵⁹, Val⁶⁰, Glu⁶¹, Ala⁶², Ala⁶³/Pro⁶³, Tyr⁶⁴, Phe⁶⁵ of the L Chain ofany of Tables 3, 4 or 5; and the amino acids Ser²⁰⁶, Leu²⁰⁷, Leu²⁰⁷ andArg²¹⁰ of the M Chain of any of Tables 3, 4 or 5.

In this screening, the quality of fit of such compounds to the bindingsite may be judged either by shape complementarity or by estimatedinteraction energy (Meng, E. C. et al., J. Coma. Chem 13:505-524(1992)).

Use of Binding Site

The design of compounds that bind to, promote or inhibit the functionalactivity of atpE according to this invention generally involvesconsideration of two factors. First, the compound must be capable ofphysically and structurally associating with atpE. Non-covalentmolecular interactions important in the association of atpE with thecompound, include hydrogen bonding, van der Waals and hydrophobicinteractions. Second, the compound must be able to assume a conformationthat allows it to associate with atpE. Although certain portions of thecompound may not directly participate in the association with atpE,those portions may still influence the overall conformation of themolecule. This, in turn, may have a significant impact on bindingaffinities, therapeutic efficacy, drug-like qualities and potency. Suchconformational requirements include the overall three-dimensionalstructure and orientation of the chemical entity or compound in relationto all or a portion of the active site or other region of atpE or thespacing between functional groups of a compound comprising severalchemical entities that directly interact with atpE.

The potential, predicted, inhibitory agonist, antagonist or bindingeffect of a ligand or other compound on atpE may be analyzed prior toits actual synthesis and testing by the use of computer modelingtechniques. If the theoretical structure of the given compound suggestsinsufficient interaction and association between it and atpE, synthesisand testing of the compound may be obviated. However, if computermodeling indicates a strong interaction, the molecule may then besynthesized and tested for its ability to interact with atpe. In thismanner, synthesis of inoperative compounds may be avoided. In somecases, inactive compounds are synthesized predicted on modeling and thentested to develop a SAR (structure-activity relationship) for compoundsinteracting with a specific region of atpE. One skilled in the art mayuse one of several methods to screen chemiacal entities fragments,compounds, or agents for their ability to associate with atpE and moreparticularly with the individual binding pockets or active sites ofatpE. This process may begin by visual inspection of, for example, theactive site on the computer screen based on the atomic coordinates ofatpE or atpE complexed with a ligand. Selected chemical entities,compounds, or agents may then be positioned in a variety oforientations, or docked within an individual binding pocket of atpE.Docking may be accomplished using software such as Quanta and Sybyl,followed by energy miniization and molecular dynamics with standardmolecular mechanics forcefields, such as CHARMM and AMBER.

Specialized computer programs may also assist in the process ofselecting chemical entities. These include but are not limited to: GRID(Goodford, P. J., “A Computational Procedure for DeterminingEnergetically Favorable Binding Sites on Biologically ImportantMacromolecules,” J. Med. Chem. 28:849-857 (1985), available from OxfordUniversity, Oxford, UK); MCSS (Miranker, A. and M. Karplus,“Functionality Maps of Binding Sites: A Multiple Copy SimultaneousSearch Method.” Proteins: Structure, Function and Genetics 11: 29-34(1991), available from Molecular Simulations, Burlington, Mass.);AUTODOCK (Goodsell, D. S, and A. J. Olsen, “Automated Docking ofSubstrates to Proteins by Simulated Annealing” Proteins: Structure.Function, and Genetics 8:195-202 (1990), available from Scripps ResearchInstitute, La Jolla, Calif.); and DOCK (Kuntz, I. D. et al., “AGeometric Approach to Macromolecule-Ligand Interactions,” J.-Mol. Biol.161:269-288 (1982), available from University of California, SanFrancisco, Calif.).

The use of software such as GRID, a program that determines probableinteraction sites between probes with various functional groupcharacteristics and the macromolecular surface, is used to analyze thesurface sites to determine structures of similar inhibiting proteins orcompounds. The GRID calculations, with suitable inhibiting groups onmolecules (e.g., protonated primary amines) as the probe, are used toidentify potential hotspots around accessible positions at suitableenergy contour levels. The program DOCK may be used to analyze an activesite or ligand binding site and suggest ligands with complementarysteric properties.

Once suitable chemical entities, compounds, or agents have beenselected, they can be assembled into a single ligand or compound orinhibitor or activator. Assembly may proceed by visual inspection of therelationship of the fragments to each other on the three-dimensionalimage. This may be followed by manual model building using software suchas Quanta or Sybyl.

Useful programs to aid in connecting the individual chemical entities,compounds, or agents include but are not limited to: CAVEAT (Bartlett,P. A. et al., “CAVEAT: A Program to Facilitate the Structure-DerivedDesign of Biologically Active Molecules.” In Molecular Recognition inChemical and Biological Problems, Special Pub., Royal Chem. Soc., 78,pp. 82-196 (1989)); 3D Database systems such as MACCS-3D (MDLInformation Systems, San Leandro, Calif. and Martin, Y. C., “3D DatabaseSearching in Drug Design”, J. Med. Chem. 35: 2145-2154 (1992); and HOOK(available from Molecular Simulations, Burlington, Mass.).

Several methodologies for searching three-dimensional databases to testpharmacophore hypotheses and select compounds for screening areavailable. These include the program CAVEAT (Bacon et al., J. Mol. Biol.225:849-858 (1992)). For instance, CAVEAT uses databases of cycliccompounds which can act as “spacers” to connect any number of chemicalfragments already positioned in the active site. This allows one skilledin the art to quickly generate hundreds of possible ways to connect thefragments already known or suspected to be necessary for tight binding.Instead of proceeding to build an inhibitor activator, agonist orantagonist of atpE in a step-wise fashion one chemical entity at a timeas described above, such compounds may be designed as a whole or “denovo” using either an empty active site or optionally including someportion(s) of a known molecules. These methods include: LUDI (Bohm,H.-J., “The Computer Program LUDI: A New Method for the De Novo Designof Enzyme Inhibitors”, J. ComR. Aid. Molec. Design, 6, pp. 61-78 (1992),available from Biosym Technologies, San Diego, Calif.); LEGEND(Nishibata, Y. and A. Itai, Tetrahedron 47:8985 (1991), available fromMolecular Simulations, Burlington, Mass.); and LeapFrog (available fromTripos Associates, St. Louis, Mo.). For instance, the program LUDI candetermine a list of interaction sites into which to place both hydrogenbonding and hydrophobic fragments. LUDI then uses a library of linkersto connect up to four different interaction sites into fragments. Thensmaller “bridging” groups such as —CH2— and —COO— are used to connectthese fragments. For example, for the enzyme DHFR, the placements of keyfunctional groups in the well-known inhibitor methotrexate werereproduced by LUDI. See also, Rotstein and Murcko, J. Med. Chem. 36:1700-1710 (1992).

Other molecular modeling techniques may also be employed in accordancewith this invention. See, e.g., Cohen, N. C. et al., “Molecular ModelingSoftware and Methods for Medicinal Chemistry, J. Med. Chem. 33:883-894(1990). See also, Navia, M. A. and M. A. Murcko, “The Use of StructuralInformation in Drug Design,” Current Opinions in Structural Biology, 2,pp. 202-210 (1992).

Once a compound has been designed or selected by the above methods, theaffinity with which that compound may bind or associate with atpE may betested and optimized by computational evaluation and/or by testingbiological activity after synthesizing the compound. Inhibitors orcompounds may interact with the atpE in more than one conformation thatis similar in overall binding energy. In those cases, the deformationenergy of binding is taken to be the difference between the energy ofthe free compound and the average energy of the conformations observedwhen the compound binds to atpE.

A compound designed or selected as binding or associating with atpE maybe further computationally optimized so that in its bound state it wouldpreferably lack repulsive electrostatic interaction with atpE. Suchnon-complementary (e.g., electrostatic) interactions include repulsivecharge-charge, dipole-dipole and charge-dipole interactions.Specifically, the sum of all electrostatic interactions between theinhibitor and atpE when the inhibitor is bound, preferably make aneutral or favorable contribution to the enthalpy of binding. Weakbinding compounds will also be designed by these methods so as todetermine SAR. See, for example, U.S. Appl. Nos. 60/275,629; 60/331,235;60/379,617; and, 10/097,249.

Specific computer software is available in the art to evaluate compounddeformation energy and electrostatic interaction. Examples of programsdesigned for such uses include: Gaussian 92, revision C (M. J. Frisch,Gaussian, Inc., Pittsburgh, Pa., COPYRGT 1992); AMBER, version 4.0 (P.A. Kollman, University of California at San Francisco, COPYRGT 1994);QUANTA/CHARMM (Molecular Simulations, Inc., Burlington, Mass. COPYRGT1994); and Insight II/Discover (Biosysm Technologies Inc., San Diego,Calif. COPYRGT 1994). Other hardware systems and software packages willbe known to those skilled in the art.

Once a compound that associates with atpE has been optimally selected ordesigned, as described above, substitutions may then be made in some ofits atoms or side groups in order to improve or modify its bindingproperties. Generally, initial substitutions are conservative, i.e., thereplacement group will have approximately the same size, shape,hydrophobicity and charge as the original group. It should, of course,be understood that components known in the art to alter conformation maybe avoided. Such substituted chemical compounds may then be analyzed forefficiency of fit to atpE by the same computer methods described indetail, above.

The present invention further provides systems, particularlycomputer-based systems, which contain the sequence and/or structurecoordinates described herein. Such systems are designed to do structuredetermination and rational drug design for atpE or for the binding sitein the F₀ part of the ATPase. The computer-based systems refer to thehardware means, software means and data storage means used to analyzethe sequence and/or structure coordinates of the present invention inany of the computer methods described in detail, above. The minimumhardware means of the computer-based system of the present inventioncomprises a central processing unit (CPU), input means, output means anddata storage means. A skilled person can readily appreciate which of thecurrently available computer-based systems are suitable for use in thepresent invention.

It is accordingly an object of the present invention to provide computerreadable data storage medium containing the structure coordinatesdescribed herein. As used herein, “computer readable data storagemedium” refers to any medium which can be read or accessed directly by acomputer. Such media include, but are not limited to: magnetic storagemedia, such as floppy disks, hard disc storage media and magnetic tape;optical storage media such as optical discs or CD-ROM; electricalstorage media such as RAM and ROM; and hybrids of these categories suchas magnetical/optical storage media.

Methods of Treatment

As already mentioned hereinbefore, it is also an object of the presentinvention to provide the use of compounds identified using any of theaforementioned screening methods in a method of treating a subject witha microbially-based infection. In general, bacterial pathogens may beclassified as either gram-positive or gram-negative pathogens.Antimicrobial compounds with activity against both gram-positive andgram-negative pathogens are generally regarded as having a broadspectrum of activity. The compounds of the present invention areregarded as active against gram-positive and/or gram-negative bacterialpathogens. In particular, the present compounds are active against atleast one gram-positive bacterium, preferably against severalgram-positive bacteria, more preferably against one or moregram-positive bacteria and/or one or more gram-negative bacteria.

Examples of gram-positive and gram-negative aerobic and anaerobicbacteria, include Staphylococci, for example S. aureus; Enterococci, forexample E. faecalis; Streptococci, for example S. pneumoniae, S. mutans,S. pyogens; Bacilli, for example Bacillus subtilis; Listeria, forexample Listeria monocytogenes; Haemophilus, for example H. influenza;Moraxella, for example M. catarrhalis; Pseudomonas, for examplePseudomonas aeruginosa; and Escherichia, for example E. coli.

Gram-positive pathogens, for example Staphylococci, Enterococci andStreptococci are particularly important because of the development ofresistant strains which are both difficult to treat and difficult toeradicate from for example a hospital environment once established.Examples of such strains are methicillin resistant Staphylococcus aureus(MRSA), methicillin resistant coagulase negative staphylococci (MRCNS),penicillin resistant Streptococcus pneumoniae and multiple resistantEnterococcus faecium.

The compounds of the present invention also show activity againstresistant bacterial strains.

The compounds of the present invention are especially active againstthose bacteria of which the viability depends on proper functioning ofF₁F₀ ATP synthase. Without being bound to any theory, it is taught thatthe activity of the present compounds lies in inhibition of the F₁F₀ ATPsynthase, in particular the inhibition of the F₀ complex of the F₁F₀ ATPsynthase, more in particular the inhibition of the proton transfer fromArg186 of the A subunit to Glu61 of the C subunit of the F₀ complex ofthe FIFO ATP synthase, leading to killing of the bacteria by depletionof the cellular ATP levels of the bacteria. The compounds identifiedusing any of the aforementioned screening methods are particularlyactive against Gram-positive bacteria, more particular mycobacteria, andmost particular against infections caused by M. africanum, M. avium, M.bovis, M. bovis-BCG, M. chelonae, M. fortuitum, M. gordonae, M.intracellulare, M. kansasii, M. microti, M. scrofulaceum, M.paratuberculosis, M. leprea, M. tuberculosis, M. ulcerans and M. ranae.

Whenever used hereinbefore or hereinafter, that the compounds can treata bacterial infection it is meant that the compounds can treat aninfection with one or more bacterial strains. When used however, inrelation to the use of DARQ J as an anti-microbial compound,anti-microbial is meant to be a compound that can treat an infectionwith one or more bacterial strains, provided that said bacterial strainsare other than mycobacteria.

Bacterial infections which may be treated by the present compoundsinclude, for example, central nervous system infections, external earinfections, infections of the middle ear, such as acute otitis media,infections of the cranial sinuses, eye infections, infections of theoral cavity, such as infections of the teeth, gums and mucosa, upperrespiratory tract infections, lower respiratory tract infections,genitourinary infections, gastrointestinal infections, gynecologicalinfections, septicemia, bone and joint infections, skin and skinstructure infections, bacterial endocarditis, burns, antibacterialprophylaxis of surgery, and antibacterial prophylaxis inimmunosuppressed patients, such as patients receiving cancerchemotherapy, or organ transplant patients.

This invention further provides a method for treating a subjectafflicted with tuberculosis comprising administering to the subject anagent that interacts with an atpE protein.

Pharmaceutical Compositions

This invention further provides for a pharmaceutical compositioncomprising an agent that interacts with an atpE protein in a cell, and apharmaceutically acceptable carrier.

Such agents may be formulated into compositions comprising an agenttogether with a pharmaceutically acceptable carrier or diluent. Theagent may in the form of a physiologically functional derivative, suchas an ester or a salt, such as an acid addition salt or basic metalsalt, or an N or S oxide. Compositions may be formulated for anysuitable route and means of administration. Pharmaceutically acceptablecarriers or diluents include those used in formulations suitable fororal, rectal, nasal, inhalable, topical (including buccal andsublingual), vaginal or parenteral (including subcutaneous,intramuscular, intravenous, intradermal, intrathecal and epidural)administration. The choice of carrier or diluent will of course dependon the proposed route of administration, which, may depend on the agentand its therapeutic purpose. The formulations may conveniently bepresented in unit dosage form and may be prepared by any of the methodswell known in the art of pharmacy. Such methods include the step ofbringing into association the active ingredient with the carrier whichconstitutes one or more accessory ingredients. In general theformulations are prepared by uniformly and intimately bringing intoassociation the active ingredient with liquid carriers or finely dividedsolid carriers or both, and then, if necessary, shaping the product.

For solid compositions, conventional non-toxic solid carriers include,for example, pharmaceutical grades of mannitol, lactose, cellulose,cellulose derivatives, starch, magnesium stearate, sodium saccharin,talcum, glucose, sucrose, magnesium carbonate, and the like may be used.The active compound as defined above may be formulated as suppositoriesusing, for example, polyalkylene glycols, acetylated triglycerides andthe like, as the carrier. Liquid pharmaceutically administrablecompositions can, for example, be prepared by dissolving, dispersing,etc, an active compound as defined above and optional pharmaceuticaladjuvants in a carrier, such as, for example, water, saline aqueousdextrose, glycerol, ethanol, and the like, to thereby form a solution orsuspension. If desired, the pharmaceutical composition to beadministered may also contain minor amounts of non-toxic auxiliarysubstances such as wetting or emulsifying agents, pH buffering agentsand the like, for example, sodium acetate, sorbitan monolaurate,triethanolamine sodium acetate, sorbitan monolaurate, triethanolamineoleate, etc. Actual methods of preparing such dosage forms are known, orwill be apparent, to those skilled in this art; for example, see Gennaroet al., Remington's Pharmaceutical Sciences, Mack Publishing Company,Easton, Pa., 18th Edition, 1990.

The composition or formulation to be administered will, in any event,contain a quantity of the active compound(s) in an amount effective toalleviate the symptoms of the subject being treated.

The exact dosage and frequency of administration of the presentcompounds depends on the particular compound used, the particularcondition being treated, the severity of the condition being treated,the age, weight, gender, diet, time of administration and generalphysical condition of the particular patient, the mode of administrationas well as other medication the individual may be taking, as is wellknown to those skilled in the art. Furthermore, it is evident that theeffective daily amount may be lowered or increased depending on theresponse of the treated subject and/or depending on the evaluation ofthe physician prescribing the compounds of the instant invention.

Dosage forms or compositions containing active ingredient in the rangeof 0.25 to 95% with the balance made up from non-toxic carrier may beprepared. Depending on the mode of administration, the pharmaceuticalcomposition will preferably comprise from 0.05 to 99% by weight, morepreferably from 0.1 to 70% by weight of the active ingredients, and,from 1 to 99.95% by weight, more preferably from 30 to 99.9 weight % ofa pharmaceutically acceptable carrier, all percentages being based onthe total composition.

For oral administration, a pharmaceutically acceptable non-toxiccomposition is formed by the incorporation of any of the normallyemployed excipients, such as, for example, pharmaceutical grades ofrnannitol, lactose, cellulose, cellulose derivatives, sodiumcrosscarmellose, starch, magnesium stearate, sodium saccharin, talcum,glucose, sucrose, magnesium, carbonate, and the like. Such compositionstake the form of solutions, suspensions, tablets, pills, capsules,powders, sustained release formulations and the like. Such compositionsmay contain 1%-95% active ingredient, more preferably 2-50%, mostpreferably 5-8%.

Parenteral administration is generally characterized by injection,either subcutaneously, intramuscularly or intravenously. Injectables canbe prepared in conventional forms, either as liquid solutions orsuspensions, solid forms suitable for solution or suspension in liquidprior to injection, or as emulsions. Suitable excipients are, forexample, water, saline, dextrose, glycerol, ethanol or the like. Inaddition, if desired, the pharmaceutical compositions to be administeredmay also contain minor amounts of non-toxic auxiliary substances such aswetting or emulsifying agents, pH buffering agents and the like, such asfor example, sodium acetate, sorbitan monolaurate, triethanolamineoleate, triethanolamine sodium acetate, etc.

The percentage of active compound contained in such parentalcompositions is highly dependent on the specific nature thereof, as wellas the activity of the compound and the needs of the subject. However,percentages of active ingredient of 0.1% to 10% in solution areemployable, and will be higher if the composition is a solid which willbe subsequently diluted to the above percentages. Preferably, thecomposition will comprise 0.2-2% of the active agent in solution.

Finally, this invention provides for an article of manufacturecomprising a packaging and a pharmaceutical agent, wherein (a) thepharmaceutical agent interacts with an atpE protein in a cell, and (b)the packaging comprises a label indicating the use of the agent fortreating a bacterial infection in a subject. In particular as ananti-mycobacterial medicine.

Throughout this description the terms “standard methods”, “standardprotocols” and “standard procedures”, when used in the context ofmolecular biology techniques, are to be understood as protocols andprocedures found in an ordinary laboratory manual such as: CurrentProtocols in Molecular Biology, editors F. Ausubel et al., John Wileyand Sons, Inc. 1994, or Sambrook, J., Fritseh, E. F. and Maniatis, T.,Molecular Cloning: A laboratory manual, 2nd Ed., Cold Spring HarborLaboratory Press, Cold Spring Harbor, N.Y. 1989.

This invention will be better understood by reference to theExperimental Details that follow, but those skilled in the art willreadily appreciate that these are only illustrative of the invention asdescribed more fully in the claims that follow thereafter. Additionally,throughout this application, various publications are cited. Thedisclosure of these publications is hereby incorporated by referenceinto this application to describe more fully the state of the art towhich this invention pertains.

EXPERIMENTAL

Using Mycobacterium smegmatis as a surrogate, we discovered a series ofDARQs with potent in vitro activity against several mycobacteria (11).To date, 20 molecules of the DARQ series have a minimal inhibitoryconcentration (MIC) below 0.5 μg/ml against Mycobacterium tuberculosisH37Rv, and for three of these the anti-mycobacterial activity wasconfirmed in the in vivo mouse model.

Structurally and mechanistically, DARQs are very different from bothfluoroquinolones (including methoxyquinolones) and other quinolineclasses, including mefloquine and its analogs, 4-methylquinolines and4-quinolylhydrazones (12-16). One of the major structural differencesbetween DARQs and other quinolone or quinoline classes is thespecificity of the functionalized lateral (3′) chain borne by the DARQclass. In addition, the lack of mycobacterial cross-resistance withexisting chemical classes points to a different mechanism of action.

The lead compound of the DARQs, hereinafter referred to as J or DARQJ(FIG. 1), was found to have an unique spectrum of potent and selectiveanti-mycobacterial activity in vitro (Table 1). The median MIC, obtainedfor the laboratory strain H37Rv and six fully susceptible isolates was0.060 μg/ml, versus 1.00 μg/ml for rifampin. J demonstrated similar invitro efficacy against M. tuberculosis clinical isolates resistant tothe first-line TB agents rifampin, streptomycin, ethambutol andpyrazinamide; and the second-line TB agent moxifloxacin. For eightclinical isolates resistant to isoniazid, the median MIC was 0.010μg/ml. The lack of cross-resistance with currently used anti-TB agentssuggested that J may retain activity against MDR-TB strains. Indeed,using the BACTEC™ culture system, a clear concentration-dependentinhibition of bacterial growth was seen when MDR-TB strains were exposedto fixed concentrations of J. Out of the 30 isolates of MDR-TB, 13 (43%)were found to be susceptible to 0.100 μg/ml of J and 17 (57%) weresusceptible to 0.010 μg/ml of J. A similar high degree of susceptibility(MIC below 0.010 μg/ml) was seen for only one of 10 additional fullydrug-susceptible strains, when tested using the BACTEC™ system, whileall strains were susceptible to 0.100 μg/ml of J.

Potent activity was also demonstrated against other mycobacterialspecies including Mycobacterium bovis and Mycobacterium kansasii, aswell as species naturally resistant to many other anti-TB agents andinvolved in opportunistic infections, such as Mycobacterium aviumcomplex (MAC), Mycobacterium abcessus, Mycobacterium fortuitum andMycobacterium marinum (Table 1).

Surprisingly, the activity of J appeared to be specific formycobacteria. J was barely active against species close to mycobacteriasuch as Corynebacterium (MIC 4.00 μg/ml) and Nocardia (MIC>4.00 μg/ml)and not active against other organisms including Gram positiveStreptococcus pneumoniae, Staphylococcus aureus—includingmethicillin-resistant strains (MIC>32 μg/ml)—and Enterococcus faecalis,or Gram negative Escherichia coli, Haemophilus influenzae, andHelicobacter pylori. Exposure of M. tuberculosis in log-phase growth toconcentrations of J at 100×MIC resulted in a 10³ log reduction inbacterial counts after 12 days, indicating that J has bactericidalactivity in vitro. The effect of J on stationary phase tubercle bacillihas not yet been studied.

Isolation of Mutants, Cross-resistance and Postulated Drug Target

By investigating mycobacterial resistance, we aimed to identify themolecular drug target and propose a mechanism of action. Resistantmutants of M. tuberculosis and M. smegmatis were derived by in vitroselection at inhibitory concentrations of J, in order to:

-   -   quantify the proportion of resistant mutants in mycobacteria        (with rifampin as a control)    -   assess the resistance pattern of resistant mutants (including        cross-/non-cross-resistance to quinolones)    -   investigate the mechanism of action.

From selection experiments, the proportion of mutants with reducedsensitivity to J was 5×10⁻⁷ and 2×10⁻⁸ at MIC×4, and 5×10⁻⁸ and 1×10⁻⁸at MIC×8 for M. tuberculosis and M. smegmatis, respectively (supportingonline text). In the case of M. tuberculosis, these proportions werecomparable to those of mutants resistant to rifampin (10⁻⁷ to 10⁻⁸) andindicates that naturally-occurring resistance to J is rare. In addition,the sensitivity of the M. tuberculosis strains resistant to J remainedunchanged to the anti-TB agents isoniazid, rifampin, streptomycin,amikacin, ethambutol and moxifloxacin. Further analysis of M.tuberculosis and M. smegmatis mutants with a reduced susceptibility to Jshowed that there were no mutations in the DNA gyrase regions gyrA andgyrB, sequences in which quinolone resistance typically develops. Thisconfirms that the molecular target for J is different from that of thefluoroquinolones.

One approach to determining the molecular target for J and inferring amechanism of action is to identify and compare resistance-conferringmutations in sensitive and resistant strains of M. tuberculosis and M.smegmatis. The genomes of the resistant M. tuberculosis strain BK12 andthe two resistant M. smegmatis strains R09 and R10, as well as theparental M. smegmatis, were sequenced to near completion. We identifiedresistance-conferring mutations by comparative analysis of the genomesequences of sensitive and resistant strains of M. tuberculosis and M.smegmatis (FIG. 2). We showed that the only gene affected in all threeindependent mutants versus corresponding parental wild-type encodes foratpE, a part of the F0 subunit of ATP synthase. This suggests that atpEis responsible for resistance to J in the mutant strains, indicatingthat J inhibits a new M. tuberculosis target, the proton pump of ATPsynthase.

Complementation studies were performed to show that the mutant atpE geneis responsible for resistance to J and by direct inference that the atpEgene product is the target of J in mycobacteria. Given the fact that itis known that all genes of the ATP synthase operon have to be expressedin a coordinated way, i.e. all genes that encode the F0 part have toexpressed from the same location, we amplified the F0 part of the operonfrom the resistant M. smegmatis strain (D32V) and selected clones thatdid not acquire additional mutations through the PCR process. Wild-typeM. smegmatis was transformed with a plasmid containing the thus selectedmutant F0 fragment. This rendered the cells resistant to J with a MICpractically identical to that of the resistant strain M. smegmatis R09(D32V). In addition, when the plasmid was re-isolated from thesetransformants and the atpE gene was sequenced, it was shown to haveremained the mutant allele (D32V).

The actual effect of DARQ J on ATP production in M. tuberculosis wasfurther demonstrated by measuring the effect of J on the total cellularATP present in the mycobacteria using the ATP Bioluminescence LuciferaseAssay Kit HS II of Roche. This assay is based on the ATP drivenconversion of D-Luciferin to Oxyluciferin that can be measured at 526nm.

Briefly, the effect of DARQ J on total ATP was tested in both wild typeM. tuberculosis and the mutant strain. DCCD which is a well knowninhibitor of ATP synthase was used as a positive control and isoniazidwhich is an inhibitor for biosynthesis of certain cell wall components,but has no effect on ATP production, was used as a negative control.

As can be seen in FIG. 3, treatment of the wild type M. tuberculosiswith DARQ J, leads to dose dependent decrease in ATP production in thesebacteria. In contrast isoniazid has no effect on ATP production. Asalready described hereinbefore, exposing these bacteria to highconcentration of the DARQ J raised the diarylquinolines resistantmutants of M. tuberculosis. When these resistant M. tuberculosis weretreated with DARQ J these bacteria did not show any decrease in the ATPproduction even at 100 times the Minimal Inhibitory Concentration (MIC)of this compound. In contrast DCCD was able to block the ATP productionin these bacilli suggesting that DARQ J and DCCD have different bindingpockets in ATP synthases.

Computer Modeling and Identification of the DARQ J Binding Region

To further investigate the different mode of action of DCCD and DARQ J,a computer generated 3D model of the ATP synthase for both the wild typeand DARQ J mutant M. tuberculosis were generated. The atomic coordinatesprovided in Tables 4 and 5 were computed by preparing a model of the 3Dstructure of the published amino acid sequences P63691 and AJ865377. Theactual DARQ J binding site was found to be located at the contact areaof the A and C subunits, more in particular around Amino Acid ‘Arg 210’of the A subunit and ‘Glu 61’ of the C subunit, as referred to in tables3, 4 or 5. This fits nicely with the results seen for the screening ofresistance-conferring mutations in sensitive and resistant strains of M.tuberculosis and M. smegmatis, described above.

The model is based on optimization of the relative placement of the A-and C helices of the ATPase structure and the orientation of the aminoacids back-bone and side-chain towards minimal computed internal strain.The geometry was obtained by means of a number of molecular dynamicssimulation cycles and molecular mechanics relaxations starting frompreviously published general helix geometry of a different organism [E.Coli PDB entry code 1C17—V. K. Rastogi and M. E. Girvin, Nature, 402,263-268 (1999)]. Molecular dynamics and geometry relaxation were bothperformed with a forcefield parameterization based on MMFF94s [Halgren,T. A. (1996), J. Comput. Chem., 17, 490-519], but any state of the artmolecular dynamics software could be employed [Berendsen, H. J. C., vander Spoel, D. and van Drunen, R., Comp. Phys. Comm. 91 (1995), 43-56;Lindahl, E., Hess, B. and van der Spoel, D., J. Mol. Mod. 7 (2001)306-317.] followed by a suitable geometry optimization [J. W. Ponder andF. M. Richards, J. Comput. Chem., 8, 1016-1024 (1987).].

The computed coordinates in the tables 3, 4 and 5 comprise the part(with 30 Angstrom radius volume) of the predicted structure of theregion considered relevant for inhibiton of the MTB ATPase activity inthese enzymes, based on the proposed mode of inhibition and on theoccurrance of resistance inducing point mutations in biological assays.

Discussion

The DARQ J is a member of a new chemical class of anti-TB agents with anMIC equal to or lower than that of reference compounds. Its spectrum isunique in its specificity to mycobacteria, including atypical speciesimportant in humans; MAC, M. kansasii and the fast growers M. fortuitumand M. abscessus. This anti-mycobacterial-specific spectrum differs fromthat of isoniazid, which has no activity against MAC. The clinical useof J will be highly targeted to the treatment of TB and mycobacterialinfections. The inability of J to inhibit non-mycobacteria shouldtranslate into less selective pressure and a lower risk of resistancedeveloping in other bacterial species, when compared with antibioticswith broader spectra (9).

The target and mechanism of action of J is different from that of otheranti-TB agents. A comparison of the sequences of ATP synthases ofdifferent bacteria and of eukaryotic ATP synthase, and in particular ofthe C chain of the F0 subunit of the ATPase complex, together with the3D modelling of the ATP synthases of the wild type and mutant M.tuberculosis, provides a rationale for the specificity of theantibacterial spectrum and, to a lesser extent, the safety profile.

The dynamics study performed on the constructed Mycobacterium ATPasemodels show that in these structures a cavity (the binding siteaccording to the atomic coordinates of Table 3) exists on the contactarea of the A and C subunits (around Amino Acid ‘Arg 210’ of the Asubunit and ‘Glu 61’ of the C subunit). The tables 4 and 5 provide thecoordinates of two studied variants of the atoms surrounding this site,and their average position. The DARQ J inhibitor is able to interferewith the normal proton transfer step involving these two amino acids byprohibiting these two amino-acids to interact. The stereospecifity ofDARQ J can be understood from the asymmetry of the predicted bindingsite; the active chiral enantiomer accommodates this cavity optimally,other forms of the compound and variants of ATPase are less wellmatched.

The binding site we have derived here is on an entirely different partof the ATPase system than DCCD (DARQs are in the membrane part of theenzyme, DCCD binding occurs approximately 90 Angstrom away inside thecell; based on the PDB structure of a Bovine ATPase crystal“1E79”—published in C. Gibbons, M. G. Montgomery, A. G. W. Leslie, J. E.Walker, Nat. Struct. Biol., 7,1055 (2000). Therefore the atoms thatcould potentially be involved with DCCD type inhibition of MTB ATPAseare not in the region listed in the coordinate tables of the bindingsite (which only just spans the membrane portion of the enzyme) and,reciprocally, this part of the enzyme involved in the DARQ J mode ofinhibition is not present in the published “1E79” structure (which onlyshows the intracellular part). This difference in binding site mayexplain the different response of M. tuberculosis observed in the invitro ATP production assay.

Notwithstanding the above, older studies with DCCD on mitochondrialATPases suggest another binding site located around an acidic amino-acidin a lipophyllic environment of the F0 region of the enzyme e.g. bySebald W, Machleidt W, Wachter E., Proc Natl Acad Sci USA. 1980February; 77(2):785-789. This binding position on mitochondrial ATPasescan be considered analogous to the one described for the Mycobacteriumspecies here.

At the same time, targeting a new mechanism ensures that currentlycirculating TB strains with resistance mutations to available treatmentsare not cross-resistant to J. It is obvious from our in vitro studiesthat J has at least as high anti-bacterial effect against MDR-TBisolates, even against those with a broad four-drug resistance, asagainst normal wild type pan-susceptible strains of M. tuberculosis.This observation is important since it clearly demonstrates that thereis no cross-resistance with existing anti-TB drugs. Given the furtheridentification of the binding pocket in the membrane part of the ATPase,the results of this study will allow further development of newanti-bacterial compounds, in particular anti-mycobacterial compoundstargeting ATP synthesis in these organisms.

REFERENCES

-   1. Global Alliance for TB Drug Development, Developing a faster TB    cure (2004; http://www.tballiance.org).-   2. E. L. Corbett et al., Arch. Intern. Med. 163, 1009 (2003).-   3. UNAIDS, AIDS epidemic update 2003 (2003;    www.unaids.org/Unaids/EN/Resources).-   4. World Health Organization, Tuberculosis (2004;    http://www.who.int/health_topics/tuberculosis/en/).-   5. R. J. O'Brien, P. P. Nunn, Am. J. Respir. Crit. Care Med. 163,    1055 (2001).-   6. World Health Organization, Tuberculosis Fact Sheet No 104 (2004;    http://www.who.int/mediacentre/factsheets/fs104/en/).-   7. A. J. Claxton, J. Cramer, C. Pierce, Clin. Ther. 23, 1296 (2001).-   8. N. Lounis et al., Antimicrob. Agents Chemother. 45, 3482 (2001).-   9. A. S. Ginsburg, J. H. Grosset, W. R. Bishai, Lancet Infect. Dis.    3, 432 (2003).-   10. C. K. Stover et al., Nature 405, 962 (2000).-   11. Guillemont J, Emile G, Patent (International Publication Number.    WO 2004/011436. International Publication Date 5 Feb., 2004).-   12. Barbachyn M R, Brickner S J, Patent (International Publication    Number: WO 93/09103, International Publication Date: 13 May 1993,    International Application Number: PCT/US92/08267, International    Filing Date: 1992).-   13. R. Jain, B. Vaitilingam, A. Nayyar, P. B. Palde, Bioorg. Med.    Chem. Lett. 13, 1051 (2003).-   14. C. M. Kunin, W. Y. Ellis, Antimicrob. Agents Chemother. 44, 848    (2000).-   15. L. Savini, L. Chiasserini, A. Gaeta, C. Pellerano, Bioorg. Med.    Chem 10, 2193 (2002).-   16. S. Vangapandu, M. Jain, R. Jain, S. Kaur, P. P. Singh, Bioorg.    Med. Chem. 12, 2501 (2004).-   17. K. Andries et al., Science 307, 223 (2005).

TABLE 1 MIC (μg/ml) Mycobacterial species Median values M. tuberculosis,H37Rv 0.030 M. tuberculosis, fully susceptible clinical isolates, 60.060 strains M. tuberculosis resistant to isoniazid, 8 strains 0.010 M.tuberculosis resistant to rifampin 0.030 M. tuberculosis resistant toisoniazid and rifampin, 2 0.030 strains M. tuberculosis resistant toisoniazid and streptomycin 0.010 M. tuberculosis resistant to ethambutol0.010 M. tuberculosis resistant to pyrazinamide 0.030 M. tuberculosisresistant to moxifloxacin, 2 strains 0.090 M. bovis 0.003 M. aviumcomplex, 7 strains 0.010 M. kansasii 0.003 M. marinum 0.003 M.fortuitum, 3 strains 0.010 M. fortuitum resistant to fluoroquinolone, 2strains 0.010 M. abscessus 0.250 M. smegmatis, 7 strains 0.007

TABLE 2 Sequence P63691 = SEQ ID No. 1 = MYCTUB C-subunit, wt SequenceAJ865377 = SEQ ID No. 2 = MYCTUB C-subunit, mutant Sequence P63654 = SEQID No. 11 = MYCTUB A-subunit, wt and mutant Amino acids surrounding thebinding site based on the atomic coordinates of Table 3 ## C-subunit 1## - A chain Ala²¹, Gly²⁵ ## C-subunit 2 ## - K chain Ala²⁴, Gly²⁷,Phe⁵³, Phe⁵⁴, Val⁵⁷, Gly⁵⁸, Glu⁶¹, Tyr⁶⁴, Phe⁶⁵ ## C-subunit 3 ## - Lchain Met¹⁷, Gly¹⁹, Gly²⁰, Ala²¹, Ile²², Gly²³, Ala²⁴, Gly²⁵, Ile²⁶,Gly²⁷, Asp²⁸, Gly²⁹, Ala³¹, Phe⁵³, Thr⁵⁶, Val⁵⁷, Gly⁵⁸, Leu⁵⁹, Val⁶⁰,Glu⁶¹, Ala⁶², Ala⁶³/Pro⁶³, Tyr⁶⁴, Phe⁶⁵. ## A subunit ## - M chainSer¹⁸², Leu¹⁸³, Leu¹⁸⁵, Arg¹⁸⁶ (having the codes Ser 206 - Leu 207 - Leu209 and Arg 210 in Tables 3)

TABLE 3 ATOM 1 N ALA A 21 6.113 −13.437 −0.893 1.00 0.00 N ATOM 2 CA ALAA 21 5.269 −13.569 0.293 1.00 0.00 C ATOM 3 C ALA A 21 3.954 −12.8070.141 1.00 0.00 C ATOM 4 O ALA A 21 2.885 −13.379 0.316 1.00 0.00 O ATOM5 CB ALA A 21 5.986 −13.138 1.571 1.00 0.00 C ATOM 6 N GLY A 25 −0.067−14.118 −0.399 1.00 0.00 N ATOM 7 CA GLY A 25 −1.020 −13.780 0.640 1.000.00 C ATOM 8 C GLY A 25 −2.283 −13.168 0.073 1.00 0.00 C ATOM 9 O GLY A25 −3.376 −13.689 0.241 1.00 0.00 O ATOM 10 N ALA K 24 −1.077 −5.39911.361 1.00 0.00 N ATOM 11 CA ALA K 24 −1.976 −5.787 12.444 1.00 0.00 CATOM 12 C ALA K 24 −3.305 −5.041 12.351 1.00 0.00 C ATOM 13 O ALA K 24−4.356 −5.642 12.491 1.00 0.00 O ATOM 14 CB ALA K 24 −1.345 −5.57713.818 1.00 0.00 C ATOM 15 N GLY K 27 −5.452 −6.238 9.570 1.00 0.00 NATOM 16 CA GLY K 27 −5.851 −7.589 9.928 1.00 0.00 C ATOM 17 C GLY K 27−7.090 −7.620 10.800 1.00 0.00 C ATOM 18 O GLY K 27 −8.059 −8.290 10.4731.00 0.00 O ATOM 19 N PHE K 53 −11.017 −14.602 19.149 1.00 0.00 N ATOM20 CA PHE K 53 −9.784 −15.282 18.770 1.00 0.00 C ATOM 21 C PHE K 53−9.069 −14.469 17.700 1.00 0.00 C ATOM 22 O PHE K 53 −7.894 −14.18817.837 1.00 0.00 O ATOM 23 CB PHE K 53 −10.007 −16.732 18.330 1.00 0.00C ATOM 24 CG PHE K 53 −8.712 −17.498 18.270 1.00 0.00 C ATOM 25 CD1 PHEK 53 −7.970 −17.568 17.070 1.00 0.00 C ATOM 26 CD2 PHE K 53 −8.215−18.156 19.416 1.00 0.00 C ATOM 27 CE1 PHE K 53 −6.755 −18.266 17.0251.00 0.00 C ATOM 28 CE2 PHE K 53 −7.002 −18.858 19.365 1.00 0.00 C ATOM29 CZ PHE K 53 −6.270 −18.911 18.171 1.00 0.00 C ATOM 30 N PHE K 54−9.831 −14.105 16.597 1.00 0.00 N ATOM 31 CA PHE K 54 −9.260 −13.36415.476 1.00 0.00 C ATOM 32 C PHE K 54 −8.595 −12.097 15.996 1.00 0.00 CATOM 33 O PHE K 54 −7.423 −11.868 15.755 1.00 0.00 O ATOM 34 CB PHE K 54−10.281 −12.983 14.388 1.00 0.00 C ATOM 35 CG PHE K 54 −10.604 −14.06613.398 1.00 0.00 C ATOM 36 CD1 PHE K 54 −9.957 −14.298 12.312 1.00 0.00C ATOM 37 CD2 PHE K 54 −11.580 −14.820 13.486 1.00 0.00 C ATOM 38 CE1PHE K 54 −10.285 −15.248 11.337 1.00 0.00 C ATOM 39 CE2 PHE K 54 −11.905−15.767 12.506 1.00 0.00 C ATOM 40 CZ PHE K 54 −11.260 −15.979 11.4301.00 0.00 C ATOM 41 N VAL K 57 −5.533 −12.244 18.563 1.00 0.00 N ATOM 42CA VAL K 57 −4.302 −12.645 17.888 1.00 0.00 C ATOM 43 C VAL K 57 −3.748−11.428 17.142 1.00 0.00 C ATOM 44 O VAL K 57 −2.561 −11.155 17.226 1.000.00 O ATOM 45 CB VAL K 57 −4.472 −13.892 16.988 1.00 0.00 C ATOM 46 CG1VAL K 57 −3.247 −14.150 16.128 1.00 0.00 C ATOM 47 CG2 VAL K 57 −4.733−15.142 17.831 1.00 0.00 C ATOM 48 N GLY K 58 −4.660 −10.700 16.389 1.000.00 N ATOM 49 CA GLY K 58 −4.292 −9.496 15.662 1.00 0.00 C ATOM 50 CGLY K 58 −3.574 −8.479 16.534 1.00 0.00 C ATOM 51 O GLY K 58 −2.502−8.003 16.192 1.00 0.00 O ATOM 52 N GLU K 61 −0.207 −9.648 18.102 1.000.00 N ATOM 53 CA GLU K 61 0.806 −9.654 17.043 1.00 0.00 C ATOM 54 C GLUK 61 1.665 −8.402 17.132 1.00 0.00 C ATOM 55 O GLU K 61 2.877 −8.49117.077 1.00 0.00 O ATOM 56 CB GLU K 61 0.193 −9.817 15.646 1.00 0.00 CATOM 57 CG GLU K 61 1.204 −9.858 14.524 1.00 0.00 C ATOM 58 CD GLU K 610.555 −10.023 13.178 1.00 0.00 C ATOM 59 OE1 GLU K 61 −0.140 −9.44412.697 1.00 0.00 O ATOM 60 OE2 GLU K 61 0.829 −10.852 12.555 1.00 0.00 OATOM 61 N TYR K 64 4.232 −8.387 19.897 1.00 0.00 N ATOM 62 CA TYR K 645.349 −9.298 19.625 1.00 0.00 C ATOM 63 C TYR K 64 6.441 −8.615 18.8161.00 0.00 C ATOM 64 O TYR K 64 7.607 −8.776 19.118 1.00 0.00 O ATOM 65CB TYR K 64 4.964 −10.610 18.922 1.00 0.00 C ATOM 66 CG TYR K 64 4.033−11.512 19.656 1.00 0.00 C ATOM 67 CD1 TYR K 64 4.038 −11.638 21.0581.00 0.00 C ATOM 68 CD2 TYR K 64 3.155 −12.305 18.914 1.00 0.00 C ATOM69 CE1 TYR K 64 3.176 −12.505 21.695 1.00 0.00 C ATOM 70 CE2 TYR K 642.306 −13.187 19.542 1.00 0.00 C ATOM 71 CZ TYR K 64 2.318 −13.27420.937 1.00 0.00 C ATOM 72 OH TYR K 64 1.474 −14.099 21.599 1.00 0.00 OATOM 73 N PHE K 65 6.031 −7.871 17.720 1.00 0.00 N ATOM 74 CA PHE K 656.997 −7.165 16.873 1.00 0.00 C ATOM 75 C PHE K 65 7.762 −6.104 17.6311.00 0.00 C ATOM 76 O PHE K 65 8.941 −5.932 17.396 1.00 0.00 O ATOM 77CB PHE K 65 6.392 −6.543 15.630 1.00 0.00 C ATOM 78 CG PHE K 65 5.963−7.560 14.648 1.00 0.00 C ATOM 79 CD1 PHE K 65 5.824 −7.882 14.293 1.000.00 C ATOM 80 CE1 PHE K 65 5.429 −8.819 13.385 1.00 0.00 C ATOM 81 CZPHE K 65 5.167 −9.448 12.818 1.00 0.00 C ATOM 82 CE2 PHE K 65 5.302−9.137 13.148 1.00 0.00 C ATOM 83 CD2 PHE K 65 5.697 −8.196 14.053 1.000.00 C ATOM 84 N MET L 17 11.107 −10.632 7.686 1.00 0.00 N ATOM 85 CAMET L 17 10.139 −10.826 8.764 1.00 0.00 C ATOM 86 C MET L 17 8.887−9.997 8.526 1.00 0.00 C ATOM 87 O MET L 17 7.804 −10.514 8.641 1.000.00 O ATOM 88 CB MET L 17 10.705 −10.543 10.163 1.00 0.00 C ATOM 89 CGMET L 17 11.688 −11.601 10.657 1.00 0.00 C ATOM 90 SD MET L 17 10.846−13.177 10.983 1.00 0.00 S ATOM 91 CE MET L 17 11.507 −14.142 9.610 1.000.00 C ATOM 92 N GLY L 19 7.665 −8.503 5.731 1.00 0.00 N ATOM 93 CA GLYL 19 6.955 −8.955 4.577 1.00 0.00 C ATOM 94 C GLY L 19 6.222 −10.2154.817 1.00 0.00 C ATOM 95 O GLY L 19 5.027 −10.326 4.589 1.00 0.00 OATOM 96 N GLY L 20 7.028 −11.189 5.274 1.00 0.00 N ATOM 97 CA GLY L 206.545 −12.472 5.462 1.00 0.00 C ATOM 98 C GLY L 20 5.400 −12.516 6.3521.00 0.00 C ATOM 99 O GLY L 20 4.328 −12.921 5.962 1.00 0.00 O ATOM 100N ALA L 21 5.696 −12.094 7.607 1.00 0.00 N ATOM 101 CA ALA L 21 4.773−12.247 8.668 1.00 0.00 C ATOM 102 C ALA L 21 3.441 −11.568 8.418 1.000.00 C ATOM 103 O ALA L 21 2.401 −12.101 8.724 1.00 0.00 O ATOM 104 CBALA L 21 5.365 −11.795 9.953 1.00 0.00 C ATOM 105 N ILE L 22 3.503−10.313 7.908 1.00 0.00 N ATOM 106 CA ILE L 22 2.293 −9.551 7.618 1.000.00 C ATOM 107 C ILE L 22 1.551 −10.212 6.464 1.00 0.00 C ATOM 108 OILE L 22 0.349 −10.406 6.550 1.00 0.00 O ATOM 109 CB ILE L 22 2.557−8.055 7.417 1.00 0.00 C ATOM 100 CG1 ILE L 22 2.757 −7.350 8.740 1.000.00 C ATOM 111 CG2 ILE L 22 1.424 −7.339 6.679 1.00 0.00 C ATOM 112 CD1ILE L 22 3.979 −7.733 9.410 1.00 0.00 C ATOM 113 N GLY L 23 2.307−10.532 5.345 1.00 0.00 N ATOM 114 CA GLY L 23 1.730 −11.131 4.153 1.000.00 C ATOM 115 C GLY L 23 0.953 −12.395 4.473 1.00 0.00 C ATOM 116 OGLY L 23 −0.212 −12.517 4.150 1.00 0.00 O ATOM 117 N ALA L 24 1.683−13.360 5.127 1.00 0.00 N ATOM 118 CA ALA L 24 1.102 −14.632 5.548 1.000.00 C ATOM 119 C ALA L 24 −0.076 −14.444 6.468 1.00 0.00 O ATOM 120 OALA L 24 −1.054 −15.158 6.348 1.00 0.00 O ATOM 121 CB ALA L 24 2.105−15.541 6.198 1.00 0.00 C ATOM 122 N GLY L 25 0.067 −13.469 7.438 1.000.00 N ATOM 123 CA GLY L 25 −0.962 −13.170 8.392 1.00 0.00 C ATOM 124 CGLY L 25 −2.268 −12.811 7.747 1.00 0.00 C ATOM 125 O GLY L 25 −3.300−13.370 8.064 1.00 0.00 O ATOM 126 N ILE L 26 −2.180 −11.796 6.833 1.000.00 N ATOM 127 CA ILE L 26 −3.331 −11.306 6.108 1.00 0.00 C ATOM 128 CILE L 26 −3.969 −12.476 5.367 1.00 0.00 C ATOM 129 O ILE L 26 −5.165−12.691 5.457 1.00 0.00 O ATOM 130 CB ILE L 26 −2.991 −10.132 5.190 1.000.00 C ATOM 131 CG1 ILE L 26 −2.576 −8.894 5.997 1.00 0.00 C ATOM 132CG2 ILE L 26 −4.165 −9.810 4.293 1.00 0.00 C ATOM 133 CD1 ILE L 26−1.882 −7.842 5.205 1.00 0.00 C ATOM 134 N GLY L 27 −3.109 −13.215 4.6021.00 0.00 N ATOM 135 CA GLY L 27 −3.538 −14.338 3.799 1.00 0.00 C ATOM136 C GLY L 27 −4.376 −15.318 4.569 1.00 0.00 C ATOM 137 O GLY L 27−5.486 −15.649 4.182 1.00 0.00 O ATOM 138 N ASP L 28 −3.765 −15.7845.701 1.00 0.00 N ATOM 139 CA ASP L 28 −4.384 −16.736 6.597 1.00 0.00 CATOM 140 C ASP L 28 −5.751 −16.267 7.012 1.00 0.00 C ATOM 141 O ASP L 28−6.700 −17.036 6.990 1.00 0.00 O ATOM 142 CB ASP L 28 −3.509 −17.0057.806 1.00 0.00 C ATOM 143 CG ASP L 28 −4.194 −17.916 8.775 1.00 0.00 CATOM 144 OD1 ASP L 28 −4.748 −17.548 9.761 1.00 0.00 O ATOM 145 OD2 ASPL 28 −4.162 −19.199 8.388 1.00 0.00 O ATOM 146 N GLY L 29 −5.813 −14.9627.433 1.00 0.00 N ATOM 147 CA GLY L 29 −7.031 −14.368 7.892 1.00 0.00 CATOM 148 C GLY L 29 −8.136 −14.525 6.883 1.00 0.00 C ATOM 149 O GLY L 29−9.135 −15.175 7.140 1.00 0.00 O ATOM 150 N ALA L 31 −8.315 −16.0313.866 1.00 0.00 N ATOM 151 CA ALA L 31 −8.577 −17.400 3.418 1.00 0.00 CATOM 152 C ALA L 31 −9.439 −18.145 4.436 1.00 0.00 C ATOM 153 O ALA L 31−10.328 −18.897 4.067 1.00 0.00 O ATOM 154 CB ALA L 31 −7.301 −18.1913.147 1.00 0.00 C ATOM 155 N PHE L 53 −8.637 −24.705 11.956 1.00 0.00 NATOM 156 CA PHE L 53 −8.164 −23.333 11.852 1.00 0.00 C ATOM 157 C PHE L53 −6.980 −23.146 12.776 1.00 0.00 C ATOM 158 O PHE L 53 −5.941 −22.71512.352 1.00 0.00 O ATOM 159 CB PHE L 53 −9.246 −22.283 12.113 1.00 0.00C ATOM 160 CG PHE L 53 −8.740 −20.882 11.934 1.00 0.00 C ATOM 161 CD1PHE L 53 −8.446 −20.390 10.644 1.00 0.00 C ATOM 162 CD2 PHE L 53 −8.535−20.038 13.053 1.00 0.00 C ATOM 163 CE1 PHE L 53 −7.950 −19.094 10.4831.00 0.00 C ATOM 164 CE2 PHE L 53 −8.049 −18.738 12.885 1.00 0.00 C ATOM165 CZ PHE L 53 −7.751 −18.269 11.601 1.00 0.00 C ATOM 166 N THR L 56−3.737 −24.941 11.832 1.00 0.00 N ATOM 167 CA THR L 56 −3.150 −24.51410.589 1.00 0.00 C ATOM 168 C THR L 56 −2.483 −23.143 10.682 1.00 0.00 CATOM 169 O THR L 56 −1.599 −22.885 9.907 1.00 0.00 O ATOM 170 CB THR L56 −4.089 −24.659 9.379 1.00 0.00 C ATOM 171 OG1 THR L 56 −3.330 −24.8368.196 1.00 0.00 O ATOM 172 CG2 THR L 56 −5.044 −23.506 9.164 1.00 0.00 CATOM 173 N VAL L 57 −2.942 −22.245 11.635 1.00 0.00 N ATOM 174 CA VAL L57 −2.286 −20.945 11.854 1.00 0.00 C ATOM 175 C VAL L 57 −0.799 −21.21212.078 1.00 0.00 C ATOM 176 O VAL L 57 0.047 −20.684 11.375 1.00 0.00 OATOM 177 CB VAL L 57 −2.896 −20.104 13.004 1.00 0.00 C ATOM 178 CG1 VALL 57 −2.085 −18.841 13.259 1.00 0.00 C ATOM 179 CG2 VAL L 57 −4.335−19.696 12.714 1.00 0.00 C ATOM 180 N GLY L 58 −0.521 −22.078 13.1131.00 0.00 N ATOM 181 CA GLY L 58 0.822 −22.415 13.487 1.00 0.00 C ATOM182 C GLY L 58 1.623 −22.917 12.328 1.00 0.00 C ATOM 183 O GLY L 582.718 −22.438 12.075 1.00 0.00 O ATOM 184 N LEU L 59 1.030 −23.95511.641 1.00 0.00 N ATOM 185 CA LEU L 59 1.708 −24.654 10.580 1.00 0.00 CATOM 186 C LEU L 59 2.185 −23.705 9.498 1.00 0.00 C ATOM 187 O LEU L 593.300 −23.786 9.049 1.00 0.00 O ATOM 188 CB LEU L 59 0.855 −25.774 9.9581.00 0.00 C ATOM 189 CG LEU L 59 0.528 −26.940 10.883 1.00 0.00 C ATOM190 CD1 LEU L 59 −0.499 −27.867 10.248 1.00 0.00 C ATOM 191 CD2 LEU L 591.757 −27.717 11.236 1.00 0.00 C ATOM 192 N VAL L 60 1.263 −22.821 9.0441.00 0.00 N ATOM 193 CA VAL L 60 1.554 −21.906 7.967 1.00 0.00 C ATOM194 C VAL L 60 2.691 −20.965 8.356 1.00 0.00 C ATOM 195 O VAL L 60 3.626−20.759 7.642 1.00 0.00 O ATOM 196 CB VAL L 60 0.309 −21.177 7.501 1.000.00 C ATOM 197 CG1 VAL L 60 0.647 −20.048 6.567 1.00 0.00 C ATOM 198CG2 VAL L 60 −0.657 −22.127 6.817 1.00 0.00 C ATOM 199 N GLU L 61 2.551−20.346 9.512 1.00 0.00 N ATOM 200 CA GLU L 61 3.536 −19.393 9.934 1.000.00 C ATOM 201 C GLU L 61 4.879 −19.960 10.193 1.00 0.00 C ATOM 202 OGLU L 61 5.880 −19.269 10.118 1.00 0.00 O ATOM 203 CB GLU L 61 3.063−18.660 11.104 1.00 0.00 C ATOM 204 CG GLU L 61 1.925 −17.819 10.7991.00 0.00 C ATOM 205 CD GLU L 61 1.586 −17.006 11.921 1.00 0.00 C ATOM206 OE1 GLU L 61 0.975 −17.516 12.864 1.00 0.00 O ATOM 207 OE2 GLU L 611.964 −15.931 11.778 1.00 0.00 O ATOM 208 N ALA L 62 4.882 −21.26110.545 1.00 0.00 N ATOM 209 CA ALA L 62 6.084 −21.956 10.944 1.00 0.00 CATOM 210 C ALA L 62 7.286 −21.785 10.048 1.00 0.00 C ATOM 211 O ALA L 628.377 −21.630 10.538 1.00 0.00 O ATOM 212 CB ALA L 62 5.859 −23.40011.174 1.00 0.00 C ATOM 213 N ALA L 63 7.092 −21.848 8.706 1.00 0.00 NATOM 214 CA ALA L 63 8.178 −21.680 7.793 1.00 0.00 C ATOM 215 C ALA L 638.991 −20.466 8.068 1.00 0.00 C ATOM 216 O ALA L 63 10.208 −20.527 8.0431.00 0.00 O ATOM 217 CB ALA L 63 7.615 −21.644 6.413 1.00 0.00 C ATOM218 N TYR L 64 8.259 −19.325 8.307 1.00 0.00 N ATOM 219 CA TYR L 648.890 −18.068 8.550 1.00 0.00 C ATOM 220 C TYR L 64 9.659 −18.103 9.8301.00 0.00 C ATOM 221 O TYR L 64 10.715 −17.566 9.914 1.00 0.00 O ATOM222 CB TYR L 64 7.922 −16.871 8.520 1.00 0.00 C ATOM 223 CG TYR L 647.295 −16.694 7.184 1.00 0.00 C ATOM 224 CD1 TYR L 64 8.019 −16.1676.135 1.00 0.00 C ATOM 225 CD2 TYR L 64 5.990 −17.079 6.950 1.00 0.00 CATOM 226 CE1 TYR L 64 7.462 −16.049 4.875 1.00 0.00 C ATOM 227 CE2 TYR L64 5.429 −16.966 5.693 1.00 0.00 C ATOM 228 CZ TYR L 64 6.164 −16.4534.661 1.00 0.00 C ATOM 229 OH TYR L 64 5.574 −16.357 3.438 1.00 0.00 OATOM 230 N PHE L 65 9.081 −18.740 10.861 1.00 0.00 N ATOM 231 CA PHE L65 9.781 −18.948 12.083 1.00 0.00 C ATOM 232 C PHE L 65 11.125 −19.65711.874 1.00 0.00 C ATOM 233 O PHE L 65 12.121 −19.278 12.457 1.00 0.00 OATOM 234 CB PHE L 65 8.919 −19.603 13.097 1.00 0.00 C ATOM 235 CG PHE L65 9.632 −20.022 14.089 1.00 0.00 C ATOM 236 CD1 PHE L 65 10.118 −19.24514.878 1.00 0.00 C ATOM 237 CE1 PHE L 65 10.820 −19.640 15.762 1.00 0.00C ATOM 238 CZ PHE L 65 11.035 −20.813 15.882 1.00 0.00 C ATOM 239 CE2PHE L 65 10.543 −21.593 15.120 1.00 0.00 C ATOM 240 CD2 PHE L 65 9.847−21.203 14.227 1.00 0.00 C ATOM 241 N SER M 206 −1.016 −25.619 19.5051.00 0.00 N ATOM 242 CA SER M 206 −0.838 −24.486 18.597 1.00 0.00 C ATOM243 C SER M 206 −0.012 −23.382 19.267 1.00 0.00 C ATOM 244 O SER M 2060.971 −22.911 18.713 1.00 0.00 O ATOM 245 CB SER M 206 −2.188 −23.96318.088 1.00 0.00 C ATOM 246 OG SER M 206 −1.997 −22.980 17.074 1.00 0.00O ATOM 247 N LEU M 207 −0.489 −22.952 20.499 1.00 0.00 N ATOM 248 CA LEUM 207 0.102 −21.823 21.215 1.00 0.00 C ATOM 249 C LEU M 207 1.546−22.138 21.608 1.00 0.00 C ATOM 250 O LEU M 207 2.423 −21.302 21.4411.00 0.00 O ATOM 251 CB LEU M 207 −0.714 −21.400 22.455 1.00 0.00 C ATOM252 CG LEU M 207 −1.865 −20.400 22.201 1.00 0.00 C ATOM 253 CD1 LEU M207 −1.340 −19.000 21.895 1.00 0.00 C ATOM 254 CD2 LEU M 207 −2.853−20.839 21.125 1.00 0.00 C ATOM 255 N LEU M 209 3.807 −24.006 20.3421.00 0.00 N ATOM 256 CA LEU M 209 4.747 −24.049 19.229 1.00 0.00 C ATOM257 C LEU M 209 5.571 −22.762 19.135 1.00 0.00 C ATOM 258 O LEU M 2096.785 −22.821 18.999 1.00 0.00 O ATOM 259 CB LEU M 209 4.036 −24.36817.902 1.00 0.00 C ATOM 260 CG LEU M 209 4.958 −24.569 16.686 1.00 0.00C ATOM 261 CD1 LEU M 209 5.927 −25.732 16.873 1.00 0.00 C ATOM 262 CD2LEU M 209 4.109 −24.811 15.444 1.00 0.00 C ATOM 263 N ARG M 210 4.854−21.566 19.167 1.00 0.00 N ATOM 264 CA ARG M 210 5.530 −20.289 18.9331.00 0.00 C ATOM 265 C ARG M 210 6.635 −20.028 19.961 1.00 0.00 C ATOM266 O ARG M 210 7.735 −19.631 19.601 1.00 0.00 O ATOM 267 CB ARG M 2104.594 −19.094 18.716 1.00 0.00 C ATOM 268 CG ARG M 210 4.089 −18.36519.945 1.00 0.00 C ATOM 269 CD ARG M 210 2.763 −18.019 20.020 1.00 0.00C ATOM 270 NE ARG M 210 2.404 −17.153 21.107 1.00 0.00 N ATOM 271 CZ ARGM 210 2.203 −17.389 22.361 1.00 0.00 C ATOM 272 NH1 ARG M 210 2.199−18.501 22.785 1.00 0.00 N ATOM 273 NH2 ARG M 210 1.994 −16.479 23.2781.00 0.00 N

TABLE 4 ATOM 1 N ALA A 21 6.345 −14.031 −0.384 1.00 0.00 N ATOM 2 CA ALAA 21 5.507 −14.175 0.805 1.00 0.00 C ATOM 3 C ALA A 21 4.183 −13.4250.676 1.00 0.00 C ATOM 4 O ALA A 21 3.126 −14.005 0.893 1.00 0.00 O ATOM5 CB ALA A 21 6.228 −13.751 2.081 1.00 0.00 C ATOM 6 N ILE A 22 4.282−12.074 0.350 1.00 0.00 N ATOM 7 CA ILE A 22 3.090 −11.221 0.235 1.000.00 C ATOM 8 C ILE A 22 2.159 −11.728 −0.869 1.00 0.00 C ATOM 9 O ILE A22 0.946 −11.670 −0.719 1.00 0.00 O ATOM 10 CB ILE A 22 3.362 −9.6870.133 1.00 0.00 C ATOM 11 CG1 ILE A 22 4.114 −9.223 −1.134 1.00 0.00 CATOM 12 CG2 ILE A 22 4.108 −9.189 1.374 1.00 0.00 C ATOM 13 CD1 ILE A 223.187 −8.776 −2.254 1.00 0.00 C ATOM 14 N GLY A 23 2.782 −12.213 −2.0161.00 0.00 N ATOM 15 CA GLY A 23 2.049 −12.734 −3.156 1.00 0.00 C ATOM 16C GLY A 23 1.095 −13.831 −2.732 1.00 0.00 C ATOM 17 O GLY A 23 −0.107−13.720 −2.928 1.00 0.00 O ATOM 18 N ALA A 24 1.708 −14.925 −2.231 1.000.00 N ATOM 19 CA ALA A 24 0.944 −16.088 −1.682 1.00 0.00 C ATOM 20 CALA A 24 −0.144 −15.660 −0.712 1.00 0.00 C ATOM 21 O ALA A 24 −1.298−16.015 −0.897 1.00 0.00 O ATOM 22 CB ALA A 24 1.797 −17.177 −1.039 1.000.00 C ATOM 23 N GLY A 25 0.280 −14.904 0.373 1.00 0.00 N ATOM 24 CA GLYA 25 −0.589 −14.587 1.491 1.00 0.00 C ATOM 25 C GLY A 25 −1.877 −13.9471.018 1.00 0.00 C ATOM 26 O GLY A 25 −2.953 −14.520 1.129 1.00 0.00 OATOM 27 N ILE A 26 −1.699 −12.685 0.473 1.00 0.00 N ATOM 28 CA ILE A 26−2.827 −11.831 0.204 1.00 0.00 C ATOM 29 C ILE A 26 −3.654 −12.542−0.969 1.00 0.00 C ATOM 30 O ILE A 26 −4.871 −12.600 −0.857 1.00 0.00 OATOM 31 CB ILE A 26 −2.401 −10.397 −0.323 1.00 0.00 C ATOM 32 CG1 ILE A26 −1.597 −9.649 0.770 1.00 0.00 C ATOM 33 CG2 ILE A 26 −3.603 −9.553−0.763 1.00 0.00 C ATOM 34 CD1 ILE A 26 −2.318 −9.454 2.099 1.00 0.00 CATOM 35 N GLY A 27 −2.942 −13.062 −2.046 1.00 0.00 N ATOM 36 CA GLY A 27−3.584 −13.678 −3.199 1.00 0.00 C ATOM 37 C GLY A 27 −4.550 −14.779−2.803 1.00 0.00 C ATOM 38 O GLY A 27 −5.716 −14.754 −3.175 1.00 0.00 OATOM 39 N ASP A 28 −3.985 −15.780 −2.024 1.00 0.00 N ATOM 40 CA ASP A 28−4.732 −16.946 −1.539 1.00 0.00 C ATOM 41 C ASP A 28 −5.998 −16.489−0.825 1.00 0.00 C ATOM 42 O ASP A 28 −7.077 −17.007 −1.083 1.00 0.00 OATOM 43 CB ASP A 28 −3.917 −17.846 −0.588 1.00 0.00 C ATOM 44 CG ASP A28 −2.860 −18.655 −1.307 1.00 0.00 C ATOM 45 OD1 ASP A 28 −2.422 −18.431−2.426 1.00 0.00 O ATOM 46 OD2 ASP A 28 −2.415 −19.668 0.523 1.00 0.00 OATOM 47 N GLY A 29 −5.802 −15.500 0.131 1.00 0.00 N ATOM 48 CA GLY A 29−6.869 −14.977 0.960 1.00 0.00 C ATOM 49 C GLY A 29 −8.039 −14.505 0.1221.00 0.00 C ATOM 50 O GLY A 29 −9.123 −15.072 0.181 1.00 0.00 O ATOM 51N LEU A 59 0.538 −20.546 −3.576 1.00 0.00 N ATOM 52 CA LEU A 59 1.616−21.013 −2.702 1.00 0.00 C ATOM 53 C LEU A 59 2.837 −21.443 −3.522 1.000.00 C ATOM 54 O LEU A 59 3.955 −21.055 −3.213 1.00 0.00 O ATOM 55 CBLEU A 59 1.142 −22.138 −1.760 1.00 0.00 C ATOM 56 CG LEU A 59 2.189−22.609 −0.730 1.00 0.00 C ATOM 57 CD1 LEU A 59 2.569 −21.503 0.256 1.000.00 C ATOM 58 CD2 LEU A 59 1.650 −23.816 0.035 1.00 0.00 C ATOM 59 NILE K 16 10.658 −2.962 11.070 1.00 0.00 N ATOM 60 CA ILE K 16 9.857−4.034 11.671 1.00 0.00 C ATOM 61 C ILE K 16 8.610 −3.416 12.307 1.000.00 C ATOM 62 O ILE K 16 7.498 −3.841 12.023 1.00 0.00 O ATOM 63 CB ILEK 16 10.670 −4.907 12.676 1.00 0.00 C ATOM 64 CG1 ILE K 16 11.731 −5.75011.933 1.00 0.00 C ATOM 65 CG2 ILE K 16 9.763 −5.838 13.492 1.00 0.00 CATOM 66 CD1 ILE K 16 12.834 −6.259 12.850 1.00 0.00 C ATOM 67 N GLY K 196.052 −1.275 9.802 1.00 0.00 N ATOM 68 CA GLY K 19 5.350 −2.226 8.9531.00 0.00 C ATOM 69 C GLY K 19 4.316 −2.998 9.750 1.00 0.00 C ATOM 70 OGLY K 19 3.177 −3.154 9.331 1.00 0.00 O ATOM 71 N GLY K 20 4.790 −3.50910.947 1.00 0.00 N ATOM 72 CA GLY K 20 3.964 −4.243 11.882 1.00 0.00 CATOM 73 C GLY K 20 2.664 −3.538 12.201 1.00 0.00 C ATOM 74 O GLY K 201.605 −4.149 12.169 1.00 0.00 O ATOM 75 N ALA K 21 2.805 −2.207 12.5611.00 0.00 N ATOM 76 CA ALA K 21 1.688 −1.384 13.006 1.00 0.00 C ATOM 77C ALA K 21 0.546 −1.397 12.001 1.00 0.00 C ATOM 78 O ALA K 21 −0.586−1.697 12.356 1.00 0.00 O ATOM 79 CB ALA K 21 2.108 0.053 13.297 1.000.00 C ATOM 80 N ILE K 22 0.886 −1.005 10.709 1.00 0.00 N ATOM 81 CA ILEK 22 −0.140 −0.867 9.671 1.00 0.00 C ATOM 82 C ILE K 22 −0.799 −2.2199.390 1.00 0.00 C ATOM 83 O ILE K 22 −2.005 −2.285 9.195 1.00 0.00 OATOM 84 CB ILE K 22 0.297 −0.092 8.393 1.00 0.00 C ATOM 85 CG1 ILE K 221.377 −0.768 7.521 1.00 0.00 C ATOM 86 CG2 ILE K 22 0.768 1.314 8.7791.00 0.00 C ATOM 87 CD1 ILE K 22 0.806 −1.667 6.434 1.00 0.00 C ATOM 88N GLY K 23 0.053 −3.318 9.365 1.00 0.00 N ATOM 89 CA GLY K 23 −0.419−4.668 9.113 1.00 0.00 C ATOM 90 C GLY K 23 −1.487 −5.090 10.101 1.000.00 C ATOM 91 O GLY K 23 −2.565 −5.521 9.715 1.00 0.00 O ATOM 92 N ALAK 24 −1.109 −4.970 11.431 1.00 0.00 N ATOM 93 CA ALA K 24 −1.982 −5.34512.540 1.00 0.00 C ATOM 94 C ALA K 24 −3.312 −4.596 12.475 1.00 0.00 CATOM 95 O ALA K 24 −4.357 −5.184 12.715 1.00 0.00 O ATOM 96 CB ALA K 24−1.317 −5.133 13.898 1.00 0.00 C ATOM 97 N GLY K 25 −3.230 −3.244 12.1581.00 0.00 N ATOM 98 CA GLY K 25 −4.396 −2.382 12.036 1.00 0.00 C ATOM 99C GLY K 25 −5.442 −2.961 11.101 1.00 0.00 C ATOM 100 O GLY K 25 −6.598−3.122 11.474 1.00 0.00 O ATOM 101 N ILE K 26 −4.967 −3.257 9.828 1.000.00 N ATOM 102 CA ILE K 26 −5.823 −3.841 8.789 1.00 0.00 C ATOM 103 CILE K 26 −6.427 −5.132 9.343 1.00 0.00 C ATOM 104 O ILE K 26 −7.637−5.300 9.305 1.00 0.00 O ATOM 105 CB ILE K 26 −5.098 −4.071 7.428 1.000.00 C ATOM 106 CG1 ILE K 26 −4.568 −2.767 6.788 1.00 0.00 C ATOM 107CG2 ILE K 26 −5.980 −4.825 6.426 1.00 0.00 C ATOM 108 CD1 ILE K 26−5.622 −1.714 6.477 1.00 0.00 C ATOM 109 N GLY K 27 −5.515 −6.056 9.8441.00 0.00 N ATOM 110 CA GLY K 27 −5.880 −7.396 10.278 1.00 0.00 C ATOM111 C GLY K 27 −7.077 −7.409 11.210 1.00 0.00 C ATOM 112 O GLY K 27−8.057 −8.096 10.950 1.00 0.00 O ATOM 113 N ASP K 28 −6.936 −6.61012.341 1.00 0.00 N ATOM 114 CA ASP K 28 −7.969 −6.501 13.377 1.00 0.00 CATOM 115 C ASP K 28 −9.319 −6.221 12.728 1.00 0.00 C ATOM 116 O ASP K 28−10.281 −6.940 12.967 1.00 0.00 O ATOM 117 CB ASP K 28 −7.684 −5.40914.428 1.00 0.00 C ATOM 118 CG ASP K 28 −6.719 −5.887 15.482 1.00 0.00 CATOM 119 OD1 ASP K 28 −5.501 −5.869 15.384 1.00 0.00 O ATOM 120 OD2 ASPK 28 −7.384 −6.394 16.550 1.00 0.00 O ATOM 121 N GLY K 29 −9.348 −5.10211.901 1.00 0.00 N ATOM 122 CA GLY K 29 −10.569 −4.615 11.289 1.00 0.00C ATOM 123 C GLY K 29 −11.212 −5.698 10.448 1.00 0.00 C ATOM 124 O GLY K29 −12.276 −6.205 10.776 1.00 0.00 O ATOM 125 N VAL K 30 −10.501 −6.0279.303 1.00 0.00 N ATOM 126 CA VAL K 30 −11.107 −6.819 8.230 1.00 0.00 CATOM 127 C VAL K 30 −11.579 −8.176 8.753 1.00 0.00 C ATOM 128 O VAL K 30−12.714 −8.565 8.512 1.00 0.00 O ATOM 129 CB VAL K 30 −10.270 −6.9376.923 1.00 0.00 C ATOM 130 CG1 VAL K 30 −10.028 −5.560 6.300 1.00 0.00 CATOM 131 CG2 VAL K 30 −8.940 −7.684 7.063 1.00 0.00 C ATOM 132 N ALA K31 −10.636 −8.920 9.451 1.00 0.00 N ATOM 133 CA ALA K 31 −10.883 −10.3149.808 1.00 0.00 C ATOM 134 C ALA K 31 −11.989 −10.412 10.852 1.00 0.00 CATOM 135 O ALA K 31 −12.931 −11.178 10.696 1.00 0.00 O ATOM 136 CB ALA K31 −9.624 −11.033 10.283 1.00 0.00 C ATOM 137 N GLY K 32 −11.816 −9.61011.974 1.00 0.00 N ATOM 138 CA GLY K 32 −12.719 −9.669 13.109 1.00 0.00C ATOM 139 C GLY K 32 −14.138 −9.365 12.675 1.00 0.00 C ATOM 140 O GLY K32 −15.039 −10.185 12.801 1.00 0.00 O ATOM 141 N PHE K 53 −10.783−14.377 18.969 1.00 0.00 N ATOM 142 CA PHE K 53 −9.482 −14.955 18.6291.00 0.00 C ATOM 143 C PHE K 53 −8.723 −14.019 17.685 1.00 0.00 C ATOM144 O PHE K 53 −7.574 −13.689 17.947 1.00 0.00 O ATOM 145 CB PHE K 53−9.600 −16.376 18.045 1.00 0.00 C ATOM 146 CG PHE K 53 −8.257 −17.05117.883 1.00 0.00 C ATOM 147 CD1 PHE K 53 −7.577 −17.020 16.639 1.00 0.00C ATOM 148 CD2 PHE K 53 −7.660 −17.740 18.968 1.00 0.00 C ATOM 149 CE1PHE K 53 −6.333 −17.661 16.487 1.00 0.00 C ATOM 150 CE2 PHE K 53 −6.416−18.382 18.810 1.00 0.00 C ATOM 151 CZ PHE K 53 −5.753 −18.344 17.5711.00 0.00 C ATOM 152 N PHE K 54 −9.409 −13.608 16.543 1.00 0.00 N ATOM153 CA PHE K 54 −8.767 −12.782 15.516 1.00 0.00 C ATOM 154 C PHE K 54−8.164 −11.541 16.176 1.00 0.00 C ATOM 155 O PHE K 54 −6.978 −11.27016.042 1.00 0.00 O ATOM 156 CB PHE K 54 −9.706 −12.321 14.380 1.00 0.00C ATOM 157 CG PHE K 54 −10.176 −13.399 13.433 1.00 0.00 C ATOM 158 CD1PHE K 54 −9.257 −14.099 12.611 1.00 0.00 C ATOM 159 CD2 PHE K 54 −11.561−13.654 13.273 1.00 0.00 C ATOM 160 CE1 PHE K 54 −9.716 −15.014 11.6441.00 0.00 C ATOM 161 CE2 PHE K 54 −12.014 −14.563 12.300 1.00 0.00 CATOM 162 CZ PHE K 54 −11.094 −15.240 11.482 1.00 0.00 C ATOM 163 N ILE K55 −9.075 −10.749 16.863 1.00 0.00 N ATOM 164 CA ILE K 55 −8.727 −9.40517.324 1.00 0.00 C ATOM 165 C ILE K 55 −7.693 −9.410 18.450 1.00 0.00 CATOM 166 O ILE K 55 −6.827 −8.544 18.477 1.00 0.00 O ATOM 167 CB ILE K55 −9.943 −8.495 17.647 1.00 0.00 C ATOM 168 CG1 ILE K 55 −10.898 −9.08118.707 1.00 0.00 C ATOM 169 CG2 ILE K 55 −10.688 −8.166 16.349 1.00 0.00C ATOM 170 CD1 ILE K 55 −12.005 −8.127 19.121 1.00 0.00 C ATOM 171 N THRK 56 −7.833 −10.391 19.426 1.00 0.00 N ATOM 172 CA THR K 56 −6.922−10.464 20.567 1.00 0.00 C ATOM 173 C THR K 56 −5.505 −10.773 20.0801.00 0.00 C ATOM 174 O THR K 56 −4.555 −10.147 20.530 1.00 0.00 O ATOM175 CB THR K 56 −7.422 −11.383 21.713 1.00 0.00 C ATOM 176 OG1 THR K 56−6.750 −11.036 22.925 1.00 0.00 O ATOM 177 CG2 THR K 56 −7.216 −12.88021.504 1.00 0.00 C ATOM 178 N VAL K 57 −5.382 −11.788 19.134 1.00 0.00 NATOM 179 CA VAL K 57 −4.079 −12.161 18.578 1.00 0.00 C ATOM 180 C VAL K57 −3.482 −10.952 17.854 1.00 0.00 C ATOM 181 O VAL K 57 −2.287 −10.72517.957 1.00 0.00 O ATOM 182 CB VAL K 57 −4.122 −13.438 17.699 1.00 0.00C ATOM 183 CG1 VAL K 57 −2.785 −13.707 17.001 1.00 0.00 C ATOM 184 CG2VAL K 57 −4.464 −14.666 18.551 1.00 0.00 C ATOM 185 N GLY K 58 −4.345−10.176 17.091 1.00 0.00 N ATOM 186 CA GLY K 58 −3.919 −8.952 16.4221.00 0.00 C ATOM 187 C GLY K 58 −3.232 −7.958 17.352 1.00 0.00 C ATOM188 O GLY K 58 −2.167 −7.439 17.046 1.00 0.00 O ATOM 189 N LEU K 59−3.928 −7.669 18.517 1.00 0.00 N ATOM 190 CA LEU K 59 −3.421 −6.73219.526 1.00 0.00 C ATOM 191 C LEU K 59 −2.069 −7.205 20.069 1.00 0.00 CATOM 192 O LEU K 59 −1.126 −6.432 20.181 1.00 0.00 O ATOM 193 CB LEU K59 −4.441 −6.520 20.664 1.00 0.00 C ATOM 194 CG LEU K 59 −4.043 −5.45321.703 1.00 0.00 C ATOM 195 CD1 LEU K 59 −3.930 −4.059 21.088 1.00 0.00C ATOM 196 CD2 LEU K 59 −5.062 −5.428 22.840 1.00 0.00 C ATOM 197 N VALK 60 −2.028 −8.531 20.469 1.00 0.00 N ATOM 198 CA VAL K 60 −0.841 −9.14921.063 1.00 0.00 C ATOM 199 C VAL K 60 0.332 −9.119 20.061 1.00 0.00 CATOM 200 O VAL K 60 1.463 −8.859 20.448 1.00 0.00 O ATOM 201 CB VAL K 60−1.166 −10.563 21.615 1.00 0.00 C ATOM 202 CG1 VAL K 60 0.084 −11.32322.031 1.00 0.00 C ATOM 203 CG2 VAL K 60 −2.098 −10.481 22.829 1.00 0.00C ATOM 204 N GLU K 61 0.026 −9.421 18.739 1.00 0.00 N ATOM 205 CA GLU K61 0.996 −9.380 17.639 1.00 0.00 C ATOM 206 C GLU K 61 1.731 −8.03917.634 1.00 0.00 C ATOM 207 O GLU K 61 2.948 −8.006 17.511 1.00 0.00 OATOM 208 CB GLU K 61 0.337 −9.677 16.274 1.00 0.00 C ATOM 209 CG GLU K61 1.291 −9.513 15.092 1.00 0.00 C ATOM 210 CD GLU K 61 0.631 −9.80713.767 1.00 0.00 C ATOM 211 OE1 GLU K 61 −0.550 −9.630 13.503 1.00 0.00O ATOM 212 OE2 GLU K 61 1.553 −10.205 12.854 1.00 0.00 O ATOM 213 N ALAK 62 0.926 −6.909 17.729 1.00 0.00 N ATOM 214 CA ALA K 62 1.483 −5.55717.728 1.00 0.00 C ATOM 215 C ALA K 62 2.586 −5.411 18.775 1.00 0.00 CATOM 216 O ALA K 62 3.669 −4.923 18.475 1.00 0.00 O ATOM 217 CB ALA K 620.419 −4.487 17.928 1.00 0.00 C ATOM 218 N ALA K 63 2.251 −5.850 20.0511.00 0.00 N ATOM 219 CA ALA K 63 3.203 −5.802 21.159 1.00 0.00 C ATOM220 C ALA K 63 4.484 −6.563 20.818 1.00 0.00 C ATOM 221 O ALA K 63 5.574−6.065 21.061 1.00 0.00 O ATOM 222 CB ALA K 63 2.615 −6.314 22.471 1.000.00 C ATOM 223 N TYR K 64 4.320 −7.827 20.262 1.00 0.00 N ATOM 224 CATYR K 64 5.460 −8.695 19.951 1.00 0.00 C ATOM 225 C TYR K 64 6.472−8.042 19.015 1.00 0.00 C ATOM 226 O TYR K 64 7.665 −8.258 19.180 1.000.00 O ATOM 227 CB TYR K 64 5.069 −10.062 19.359 1.00 0.00 C ATOM 228 CGTYR K 64 4.322 −11.015 20.266 1.00 0.00 C ATOM 229 CD1 TYR K 64 4.486−11.028 21.679 1.00 0.00 C ATOM 230 CD2 TYR K 64 3.483 −11.993 19.6781.00 0.00 C ATOM 231 CE1 TYR K 64 3.829 −11.984 22.471 1.00 0.00 C ATOM232 CE2 TYR K 64 2.857 −12.979 20.459 1.00 0.00 C ATOM 233 CZ TYR K 643.033 −12.965 21.859 1.00 0.00 C ATOM 234 OH TYR K 64 2.416 −13.90222.671 1.00 0.00 O ATOM 235 N PHE K 65 5.971 −7.269 17.972 1.00 0.00 NATOM 236 CA PHE K 65 6.881 −6.566 17.058 1.00 0.00 C ATOM 237 C PHE K 657.823 −5.649 17.839 1.00 0.00 C ATOM 238 O PHE K 65 9.014 −5.614 17.5601.00 0.00 O ATOM 239 CB PHE K 65 6.180 −5.739 15.966 1.00 0.00 C ATOM240 CG PHE K 65 5.527 −6.570 14.890 1.00 0.00 C ATOM 241 CD1 PHE K 654.136 −6.471 14.655 1.00 0.00 C ATOM 242 CE1 PHE K 65 3.536 −7.17413.596 1.00 0.00 C ATOM 243 CZ PHE K 65 4.312 −8.000 12.767 1.00 0.00 CATOM 244 CE2 PHE K 65 5.693 −8.121 12.994 1.00 0.00 C ATOM 245 CD2 PHE K65 6.298 −7.409 14.046 1.00 0.00 C ATOM 246 N ASN K 67 8.600 −5.83721.135 1.00 0.00 N ATOM 247 CA ASN K 67 9.499 −6.640 21.975 1.00 0.00 CATOM 248 C ASN K 67 10.712 −7.094 21.170 1.00 0.00 C ATOM 249 O ASN K 6711.841 −6.910 21.603 1.00 0.00 O ATOM 250 CB ASN K 67 8.840 −7.87522.619 1.00 0.00 C ATOM 251 CG ASN K 67 7.877 −7.498 23.726 1.00 0.00 CATOM 252 OD1 ASN K 67 6.675 −7.388 23.534 1.00 0.00 O ATOM 253 ND2 ASN K67 8.480 −7.263 24.941 1.00 0.00 N ATOM 254 N LEU K 68 10.429 −7.74419.975 1.00 0.00 N ATOM 255 CA LEU K 68 11.456 −8.357 19.131 1.00 0.00 CATOM 256 C LEU K 68 12.495 −7.303 18.752 1.00 0.00 C ATOM 257 O LEU K 6813.684 −7.496 18.968 1.00 0.00 O ATOM 258 CB LEU K 68 10.830 −9.06617.909 1.00 0.00 C ATOM 259 CG LEU K 68 11.796 −9.975 17.120 1.00 0.00 CATOM 260 CD1 LEU K 68 11.014 −11.105 16.449 1.00 0.00 C ATOM 261 CD2 LEUK 68 12.577 −9.208 16.051 1.00 0.00 C ATOM 262 N GLY L 14 14.989 −7.7158.662 1.00 0.00 N ATOM 263 CA GLY L 14 13.793 −6.924 8.905 1.00 0.00 CATOM 264 C GLY L 14 12.803 −7.025 7.757 1.00 0.00 C ATOM 265 O GLY L 1411.628 −7.291 7.964 1.00 0.00 O ATOM 266 N ILE L 16 12.496 −9.152 5.0911.00 0.00 N ATOM 267 CA ILE L 16 11.861 −10.451 4.837 1.00 0.00 C ATOM268 C ILE L 16 10.744 −10.700 5.848 1.00 0.00 C ATOM 269 O ILE L 169.660 −11.122 5.468 1.00 0.00 O ATOM 270 CB ILE L 16 12.856 −11.6344.660 1.00 0.00 C ATOM 271 CG1 ILE L 16 12.208 −12.880 4.017 1.00 0.00 CATOM 272 CG2 ILE L 16 13.681 −11.997 5.896 1.00 0.00 C ATOM 273 CD1 ILEL 16 11.497 −13.860 4.942 1.00 0.00 C ATOM 274 N MET L 17 11.051 −10.4477.180 1.00 0.00 N ATOM 275 CA MET L 17 10.081 −10.700 8.246 1.00 0.00 CATOM 276 C MET L 17 8.818 −9.866 8.100 1.00 0.00 C ATOM 277 O MET L 177.742 −10.352 8.419 1.00 0.00 O ATOM 278 CB MET L 17 10.651 −10.5239.664 1.00 0.00 C ATOM 279 CG MET L 17 11.609 −11.637 10.084 1.00 0.00 CATOM 280 SD MET L 17 10.743 −13.242 10.212 1.00 0.00 S ATOM 281 CE MET L17 11.465 −14.067 8.772 1.00 0.00 C ATOM 282 N ALA L 18 8.969 −8.5647.642 1.00 0.00 N ATOM 283 CA ALA L 18 7.807 −7.726 7.352 1.00 0.00 CATOM 284 C ALA L 18 6.915 −8.420 6.322 1.00 0.00 C ATOM 285 O ALA L 185.715 −8.548 6.522 1.00 0.00 O ATOM 286 CB ALA L 18 8.183 −6.319 6.8951.00 0.00 C ATOM 287 N GLY L 19 7.564 −8.879 5.182 1.00 0.00 N ATOM 288CA GLY L 19 6.870 −9.586 4.117 1.00 0.00 C ATOM 289 C GLY L 19 6.019−10.723 4.654 1.00 0.00 C ATOM 290 O GLY L 19 4.826 −10.794 4.389 1.000.00 O ATOM 291 N GLY L 20 6.714 −11.641 5.428 1.00 0.00 N ATOM 292 CAGLY L 20 6.091 −12.813 6.017 1.00 0.00 C ATOM 293 C GLY L 20 4.924−12.424 6.902 1.00 0.00 C ATOM 294 O GLY L 20 3.775 −12.706 6.596 1.000.00 O ATOM 295 N ALA L 21 5.288 −11.749 8.053 1.00 0.00 N ATOM 296 CAALA L 21 4.370 −11.537 9.169 1.00 0.00 C ATOM 297 C ALA L 21 3.087−10.818 8.764 1.00 0.00 C ATOM 298 O ALA L 21 2.008 −11.206 9.192 1.000.00 O ATOM 299 CB ALA L 21 5.030 −10.783 10.317 1.00 0.00 C ATOM 300 NILE L 22 3.250 −9.680 7.980 1.00 0.00 N ATOM 301 CA ILE L 22 2.109−8.859 7.573 1.00 0.00 C ATOM 302 C ILE L 22 1.336 −9.638 6.508 1.000.00 C ATOM 303 O ILE L 22 0.144 −9.865 6.661 1.00 0.00 O ATOM 304 CBILE L 22 2.489 −7.415 7.124 1.00 0.00 C ATOM 305 CG1 ILE L 22 2.941−6.542 8.320 1.00 0.00 C ATOM 306 CG2 ILE L 22 1.297 −6.718 6.455 1.000.00 C ATOM 307 CD1 ILE L 22 4.411 −6.675 8.676 1.00 0.00 C ATOM 308 NGLY L 23 2.058 −10.000 5.378 1.00 0.00 N ATOM 309 CA GLY L 23 1.420−10.535 4.184 1.00 0.00 C ATOM 310 C GLY L 23 0.632 −11.791 4.483 1.000.00 C ATOM 311 O GLY L 23 −0.575 −11.846 4.285 1.00 0.00 O ATOM 312 NALA L 24 1.408 −12.831 4.972 1.00 0.00 N ATOM 313 CA ALA L 24 0.840−14.126 5.333 1.00 0.00 C ATOM 314 C ALA L 24 −0.200 −13.997 6.437 1.000.00 C ATOM 315 O ALA L 24 −1.182 −14.722 6.421 1.00 0.00 O ATOM 316 CBALA L 24 1.894 −15.147 5.746 1.00 0.00 C ATOM 317 N GLY L 25 0.065−13.074 7.441 1.00 0.00 N ATOM 318 CA GLY L 25 −0.835 −12.872 8.565 1.000.00 C ATOM 319 C GLY L 25 −2.244 −12.510 8.132 1.00 0.00 C ATOM 320 OGLY L 25 −3.203 −13.173 8.505 1.00 0.00 O ATOM 321 N ILE L 26 −2.329−11.374 7.337 1.00 0.00 N ATOM 322 CA ILE L 26 −3.608 −10.852 6.834 1.000.00 C ATOM 323 C ILE L 26 −4.264 −11.948 5.991 1.00 0.00 C ATOM 324 OILE L 26 −5.440 −12.236 6.166 1.00 0.00 O ATOM 325 CB ILE L 26 −3.469−9.511 6.056 1.00 0.00 C ATOM 326 CG1 ILE L 26 −3.005 −8.379 7.001 1.000.00 C ATOM 327 CG2 ILE L 26 −4.794 −9.115 5.386 1.00 0.00 C ATOM 328CD1 ILE L 26 −2.547 −7.131 6.263 1.00 0.00 C ATOM 329 N GLY L 27 −3.444−12.534 5.034 1.00 0.00 N ATOM 330 CA GLY L 27 −3.895 −13.566 4.116 1.000.00 C ATOM 331 C GLY L 27 −4.612 −14.699 4.822 1.00 0.00 C ATOM 332 OGLY L 27 −5.743 −15.030 4.495 1.00 0.00 O ATOM 333 N ASP L 28 −3.866−15.300 5.825 1.00 0.00 N ATOM 334 CA ASP L 28 −4.342 −16.404 6.656 1.000.00 C ATOM 335 C ASP L 28 −5.678 −16.044 7.295 1.00 0.00 C ATOM 336 OASP L 28 −6.607 −16.838 7.255 1.00 0.00 O ATOM 337 CB ASP L 28 −3.304−16.805 7.718 1.00 0.00 C ATOM 338 CG ASP L 28 −3.834 −17.837 8.680 1.000.00 C ATOM 339 OD1 ASP L 28 −4.192 −17.594 9.822 1.00 0.00 O ATOM 340OD2 ASP L 28 −3.898 −19.067 8.109 1.00 0.00 O ATOM 341 N GLY L 29 −5.735−14.805 7.918 1.00 0.00 N ATOM 342 CA GLY L 29 −6.922 −14.317 8.598 1.000.00 C ATOM 343 C GLY L 29 −8.156 −14.418 7.720 1.00 0.00 C ATOM 344 OGLY L 29 −9.113 −15.099 8.061 1.00 0.00 O ATOM 345 N VAL L 30 −8.091−13.675 6.548 1.00 0.00 N ATOM 346 CA VAL L 30 −9.233 −13.575 5.632 1.000.00 C ATOM 347 C VAL L 30 −9.587 −14.913 4.961 1.00 0.00 C ATOM 348 OVAL L 30 −10.748 −15.158 4.661 1.00 0.00 O ATOM 349 CB VAL L 30 −9.143−12.412 4.611 1.00 0.00 C ATOM 350 CG1 VAL L 30 −9.013 −11.058 5.3101.00 0.00 C ATOM 351 CG2 VAL L 30 −8.035 −12.576 3.573 1.00 0.00 C ATOM352 N ALA L 31 −8.539 −15.791 4.710 1.00 0.00 N ATOM 353 CA ALA L 31−8.767 −17.161 4.238 1.00 0.00 C ATOM 354 C ALA L 31 −9.633 −17.9385.230 1.00 0.00 C ATOM 355 O ALA L 31 −10.516 −18.686 4.834 1.00 0.00 OATOM 356 CB ALA L 31 −7.472 −17.928 3.981 1.00 0.00 C ATOM 357 N GLY L32 −9.321 −17.746 6.570 1.00 0.00 N ATOM 358 CA GLY L 32 −10.106 −18.2957.661 1.00 0.00 C ATOM 359 C GLY L 32 −11.567 −17.924 7.538 1.00 0.00 CATOM 360 O GLY L 32 −12.428 −18.788 7.620 1.00 0.00 O ATOM 361 N THR L51 −11.764 −26.332 14.771 1.00 0.00 N ATOM 362 CA THR L 51 −10.467−26.987 14.935 1.00 0.00 C ATOM 363 C THR L 51 −9.452 −26.599 13.8481.00 0.00 C ATOM 364 O THR L 51 −8.351 −26.190 14.199 1.00 0.00 O ATOM365 CB THR L 51 −10.589 −28.519 15.109 1.00 0.00 C ATOM 366 OG1 THR L 51−11.578 −28.792 16.105 1.00 0.00 O ATOM 367 CG2 THR L 51 −9.288 −29.15715.580 1.00 0.00 C ATOM 368 N PRO L 52 −9.797 −26.799 12.499 1.00 0.00 NATOM 369 CA PRO L 52 −8.818 −26.678 11.427 1.00 0.00 C ATOM 370 C PRO L52 −8.028 −25.377 11.428 1.00 0.00 C ATOM 371 O PRO L 52 −6.825 −25.38811.203 1.00 0.00 O ATOM 372 CB PRO L 52 −9.592 −26.833 10.125 1.00 0.00C ATOM 373 CG PRO L 52 −10.863 −27.542 10.527 1.00 0.00 C ATOM 374 CDPRO L 52 −11.104 −27.123 11.962 1.00 0.00 C ATOM 375 N PHE L 53 −8.777−24.222 11.638 1.00 0.00 N ATOM 376 CA PHE L 53 −8.158 −22.904 11.5751.00 0.00 C ATOM 377 C PHE L 53 −7.070 −22.835 12.640 1.00 0.00 C ATOM378 O PHE L 53 −5.919 −22.563 12.328 1.00 0.00 O ATOM 379 CB PHE L 53−9.165 −21.749 11.710 1.00 0.00 C ATOM 380 CG PHE L 53 −8.486 −20.40611.576 1.00 0.00 C ATOM 381 CD1 PHE L 53 −8.068 −19.938 10.308 1.00 0.00C ATOM 382 CD2 PHE L 53 −8.232 −19.601 12.715 1.00 0.00 C ATOM 383 CE1PHE L 53 −7.415 −18.699 10.186 1.00 0.00 C ATOM 384 CE2 PHE L 53 −7.598−18.352 12.585 1.00 0.00 C ATOM 385 CZ PHE L 53 −7.185 −17.903 11.3201.00 0.00 C ATOM 386 N PHE L 54 −7.493 −23.069 13.942 1.00 0.00 N ATOM387 CA PHE L 54 −6.624 −22.780 15.082 1.00 0.00 C ATOM 388 C PHE L 54−5.283 −23.500 14.934 1.00 0.00 C ATOM 389 O PHE L 54 −4.238 −22.89915.149 1.00 0.00 O ATOM 390 CB PHE L 54 −7.258 −23.112 16.446 1.00 0.00C ATOM 391 CG PHE L 54 −8.520 −22.346 16.780 1.00 0.00 C ATOM 392 CD1PHE L 54 −8.627 −20.946 16.577 1.00 0.00 C ATOM 393 CD2 PHE L 54 −9.626−23.027 17.347 1.00 0.00 C ATOM 394 CE1 PHE L 54 −9.810 −20.260 16.9051.00 0.00 C ATOM 395 CE2 PHE L 54 −10.796 −22.330 17.701 1.00 0.00 CATOM 396 CZ PHE L 54 −10.892 −20.948 17.473 1.00 0.00 C ATOM 397 N ILE L55 −5.352 −24.850 14.595 1.00 0.00 N ATOM 398 CA ILE L 55 −4.139 −25.66614.492 1.00 0.00 C ATOM 399 C ILE L 55 −3.201 −25.129 13.402 1.00 0.00 CATOM 400 O ILE L 55 −2.003 −25.002 13.627 1.00 0.00 O ATOM 401 CB ILE L55 −4.402 −27.198 14.419 1.00 0.00 C ATOM 402 CG1 ILE L 55 −3.088−27.977 14.635 1.00 0.00 C ATOM 403 CG2 ILE L 55 −5.106 −27.651 13.1361.00 0.00 C ATOM 404 CD1 ILE L 55 −3.303 −29.446 14.966 1.00 0.00 C ATOM405 N THR L 56 −3.789 −24.860 12.169 1.00 0.00 N ATOM 406 CA THR L 56−2.977 −24.541 10.996 1.00 0.00 C ATOM 407 C THR L 56 −2.190 −23.22911.131 1.00 0.00 C ATOM 408 O THR L 56 −1.166 −23.089 10.475 1.00 0.00 OATOM 409 CB THR L 56 −3.767 −24.642 9.664 1.00 0.00 C ATOM 410 OG1 THR L56 −2.866 −24.908 8.586 1.00 0.00 O ATOM 411 CG2 THR L 56 −4.606 −23.4219.294 1.00 0.00 C ATOM 412 N VAL L 57 −2.720 −22.244 11.970 1.00 0.00 NATOM 413 CA VAL L 57 −2.067 −20.936 12.149 1.00 0.00 C ATOM 414 C VAL L57 −0.599 −21.186 12.511 1.00 0.00 C ATOM 415 O VAL L 57 0.303 −20.73811.815 1.00 0.00 O ATOM 416 CB VAL L 57 −2.746 −20.000 13.195 1.00 0.00C ATOM 417 CG1 VAL L 57 −1.993 −18.675 13.324 1.00 0.00 C ATOM 418 CG2VAL L 57 −4.196 −19.681 12.839 1.00 0.00 C ATOM 419 N GLY L 58 −0.405−21.929 13.671 1.00 0.00 N ATOM 420 CA GLY L 58 0.911 −22.161 14.2391.00 0.00 C ATOM 421 C GLY L 58 1.842 −22.808 13.236 1.00 0.00 C ATOM422 O GLY L 58 2.952 −22.341 13.023 1.00 0.00 O ATOM 423 N LEU L 591.332 −23.958 12.645 1.00 0.00 N ATOM 424 CA LEU L 59 2.136 −24.81911.776 1.00 0.00 C ATOM 425 C LEU L 59 2.757 −24.020 10.627 1.00 0.00 CATOM 426 O LEU L 59 3.950 −24.127 10.374 1.00 0.00 O ATOM 427 CB LEU L59 1.344 −26.017 11.210 1.00 0.00 C ATOM 428 CG LEU L 59 0.863 −27.03412.268 1.00 0.00 C ATOM 429 CD1 LEU L 59 −0.081 −28.045 11.621 1.00 0.00C ATOM 430 CD2 LEU L 59 2.027 −27.772 12.932 1.00 0.00 C ATOM 431 N VALL 60 1.872 −23.244 9.886 1.00 0.00 N ATOM 432 CA VAL L 60 2.291 −22.5218.680 1.00 0.00 C ATOM 433 C VAL L 60 3.333 −21.474 9.071 1.00 0.00 CATOM 434 O VAL L 60 4.419 −21.440 8.507 1.00 0.00 O ATOM 435 CB VAL L 601.098 −21.909 7.895 1.00 0.00 C ATOM 436 CG1 VAL L 60 1.551 −20.9646.776 1.00 0.00 C ATOM 437 CG2 VAL L 60 0.246 −23.017 7.273 1.00 0.00 CATOM 438 N GLU L 61 2.931 −20.563 10.039 1.00 0.00 N ATOM 439 CA GLU L61 3.735 −19.381 10.357 1.00 0.00 C ATOM 440 C GLU L 61 5.107 −19.72210.949 1.00 0.00 C ATOM 441 O GLU L 61 6.043 −18.942 10.816 1.00 0.00 OATOM 442 CB GLU L 61 2.988 −18.378 11.246 1.00 0.00 C ATOM 443 CG GLU L61 1.789 −17.773 10.507 1.00 0.00 C ATOM 444 CD GLU L 61 1.165 −16.63711.308 1.00 0.00 C ATOM 445 OE1 GLU L 61 0.658 −16.959 12.417 1.00 0.00O ATOM 446 OE2 GLU L 61 1.212 −15.497 10.769 1.00 0.00 O ATOM 447 N ALAL 62 5.207 −20.935 11.625 1.00 0.00 N ATOM 448 CA ALA L 62 6.476 −21.44312.148 1.00 0.00 C ATOM 449 C ALA L 62 7.593 −21.430 11.110 1.00 0.00 CATOM 450 O ALA L 62 8.733 −21.152 11.454 1.00 0.00 O ATOM 451 CB ALA L62 6.351 −22.844 12.734 1.00 0.00 C ATOM 452 N ALA L 63 7.235 −21.7779.810 1.00 0.00 N ATOM 453 CA ALA L 63 8.205 −21.820 8.714 1.00 0.00 CATOM 454 C ALA L 63 9.043 −20.543 8.636 1.00 0.00 C ATOM 455 O ALA L 6310.257 −20.607 8.499 1.00 0.00 O ATOM 456 CB ALA L 63 7.547 −22.0837.362 1.00 0.00 C ATOM 457 N TYR L 64 8.333 −19.349 8.701 1.00 0.00 NATOM 458 CA TYR L 64 9.006 −18.049 8.621 1.00 0.00 C ATOM 459 C TYR L 6410.000 −17.881 9.768 1.00 0.00 C ATOM 460 O TYR L 64 11.097 −17.3799.562 1.00 0.00 O ATOM 461 CB TYR L 64 8.042 −16.849 8.590 1.00 0.00 CATOM 462 CG TYR L 64 7.194 −16.820 7.341 1.00 0.00 C ATOM 463 CD1 TYR L64 7.770 −16.499 6.085 1.00 0.00 C ATOM 464 CD2 TYR L 64 5.811 −17.1187.404 1.00 0.00 C ATOM 465 CE1 TYR L 64 6.990 −16.502 4.914 1.00 0.00 CATOM 466 CE2 TYR L 64 5.024 −17.125 6.238 1.00 0.00 C ATOM 467 CZ TYR L64 5.615 −16.821 4.997 1.00 0.00 C ATOM 468 OH TYR L 64 4.807 −16.8473.870 1.00 0.00 O ATOM 469 N PHE L 65 9.571 −18.285 11.026 1.00 0.00 NATOM 470 CA PHE L 65 10.456 −18.198 12.188 1.00 0.00 C ATOM 471 C PHE L65 11.751 −19.001 11.982 1.00 0.00 C ATOM 472 O PHE L 65 12.807 −18.57212.428 1.00 0.00 O ATOM 473 CB PHE L 65 9.751 −18.584 13.503 1.00 0.00 CATOM 474 CG PHE L 65 10.605 −18.264 14.707 1.00 0.00 C ATOM 475 CD1 PHEL 65 10.790 −16.921 15.123 1.00 0.00 C ATOM 476 CE1 PHE L 65 11.649−16.616 16.194 1.00 0.00 C ATOM 477 CZ PHE L 65 12.328 −17.647 16.8671.00 0.00 C ATOM 478 CE2 PHE L 65 12.135 −18.985 16.481 1.00 0.00 C ATOM479 CD2 PHE L 65 11.277 −19.295 15.410 1.00 0.00 C ATOM 480 N ILE L 6611.648 −20.219 11.314 1.00 0.00 N ATOM 481 CA ILE L 66 12.834 −21.03911.020 1.00 0.00 C ATOM 482 C ILE L 66 13.831 −20.203 10.207 1.00 0.00 CATOM 483 O ILE L 66 15.012 −20.185 10.527 1.00 0.00 O ATOM 484 CB ILE L66 12.536 −22.402 10.326 1.00 0.00 C ATOM 485 CG1 ILE L 66 11.537−23.293 11.099 1.00 0.00 C ATOM 486 CG2 ILE L 66 13.824 −23.190 10.0541.00 0.00 C ATOM 487 CD1 ILE L 66 11.915 −23.605 12.541 1.00 0.00 C ATOM488 N ASN L 67 13.319 −19.523 9.103 1.00 0.00 N ATOM 489 CA ASN L 6714.170 −18.671 8.257 1.00 0.00 C ATOM 490 C ASN L 67 14.893 −17.6219.100 1.00 0.00 C ATOM 491 O ASN L 67 16.086 −17.414 8.918 1.00 0.00 OATOM 492 CB ASN L 67 13.433 −17.956 7.109 1.00 0.00 C ATOM 493 CG ASN L67 12.966 −18.928 6.045 1.00 0.00 C ATOM 494 OD1 ASN L 67 11.854 −19.4336.070 1.00 0.00 O ATOM 495 ND2 ASN L 67 13.914 −19.210 5.086 1.00 0.00 NATOM 496 N LEU L 68 14.100 −16.932 10.018 1.00 0.00 N ATOM 497 CA LEU L68 14.623 −15.890 10.911 1.00 0.00 C ATOM 498 C LEU L 68 15.848 −16.46111.624 1.00 0.00 C ATOM 499 O LEU L 68 16.945 −15.935 11.495 1.00 0.00 OATOM 500 CB LEU L 68 13.567 −15.371 11.923 1.00 0.00 C ATOM 501 CG LEU L68 13.797 −13.942 12.458 1.00 0.00 C ATOM 502 CD1 LEU L 68 12.687−13.579 13.446 1.00 0.00 C ATOM 503 CD2 LEU L 68 15.146 −13.745 13.1461.00 0.00 C ATOM 504 N ALA L 69 15.599 −17.586 12.403 1.00 0.00 N ATOM505 CA ALA L 69 16.590 −18.175 13.295 1.00 0.00 C ATOM 506 C ALA L 6917.875 −18.501 12.545 1.00 0.00 C ATOM 507 O ALA L 69 18.956 −18.14612.993 1.00 0.00 O ATOM 508 CB ALA L 69 16.062 −19.423 13.999 1.00 0.00C ATOM 509 N SER M 199 −10.235 −24.828 20.448 1.00 0.00 N ATOM 510 CASER M 199 −10.460 −26.277 20.457 1.00 0.00 C ATOM 511 C SER M 199 −9.383−26.909 21.342 1.00 0.00 C ATOM 512 O SER M 199 −8.255 −26.439 21.4361.00 0.00 O ATOM 513 CB SER M 199 −10.426 −26.831 19.028 1.00 0.00 CATOM 514 OG SER M 199 −10.782 −28.211 19.040 1.00 0.00 O ATOM 515 N ALAM 202 −6.359 −28.395 19.399 1.00 0.00 N ATOM 516 CA ALA M 202 −5.624−27.448 18.568 1.00 0.00 C ATOM 517 C ALA M 202 −4.672 −26.589 19.3891.00 0.00 C ATOM 518 O ALA M 202 −3.496 −26.490 19.067 1.00 0.00 O ATOM519 CB ALA M 202 −6.548 −26.552 17.752 1.00 0.00 C ATOM 520 N LYS M 203−5.259 −25.887 20.436 1.00 0.00 N ATOM 521 CA LYS M 203 −4.565 −24.77621.085 1.00 0.00 C ATOM 522 C LYS M 203 −3.211 −25.173 21.673 1.00 0.00C ATOM 523 O LYS M 203 −2.244 −24.472 21.408 1.00 0.00 O ATOM 524 CB LYSM 203 −5.421 −24.006 22.104 1.00 0.00 C ATOM 525 CG LYS M 203 −6.351−23.021 21.397 1.00 0.00 C ATOM 526 CD LYS M 203 −7.207 −22.239 22.3911.00 0.00 C ATOM 527 CE LYS M 203 −7.942 −21.073 21.731 1.00 0.00 C ATOM528 NZ LYS M 203 −8.880 −21.518 20.704 1.00 0.00 N ATOM 529 N PRO M 204−3.121 −26.287 22.520 1.00 0.00 N ATOM 530 CA PRO M 204 −1.857 −26.68823.113 1.00 0.00 C ATOM 531 C PRO M 204 −0.698 −26.719 22.124 1.00 0.00C ATOM 532 O PRO M 204 0.311 −26.064 22.348 1.00 0.00 O ATOM 533 CB PROM 204 −2.120 −28.029 23.781 1.00 0.00 C ATOM 534 CG PRO M 204 −3.599−27.984 24.098 1.00 0.00 C ATOM 535 CD PRO M 204 −4.203 −27.116 23.0101.00 0.00 C ATOM 536 N ILE M 205 −0.871 −27.523 21.001 1.00 0.00 N ATOM537 CA ILE M 205 0.201 −27.693 20.012 1.00 0.00 C ATOM 538 C ILE M 2050.518 −26.340 19.365 1.00 0.00 C ATOM 539 O ILE M 205 1.669 −25.92419.342 1.00 0.00 O ATOM 540 CB ILE M 205 −0.021 −28.884 19.030 1.00 0.00C ATOM 541 CG1 ILE M 205 1.238 −29.236 18.204 1.00 0.00 C ATOM 542 CG2ILE M 205 −1.273 −28.799 18.151 1.00 0.00 C ATOM 543 CD1 ILE M 205 1.490−28.405 16.949 1.00 0.00 C ATOM 544 N SER M 206 −0.566 −25.670 18.8161.00 0.00 N ATOM 545 CA SER M 206 −0.425 −24.504 17.945 1.00 0.00 C ATOM546 C SER M 206 0.370 −23.401 18.645 1.00 0.00 C ATOM 547 O SER M 2061.352 −22.898 18.114 1.00 0.00 O ATOM 548 CB SER M 206 −1.797 −24.00517.472 1.00 0.00 C ATOM 549 OG SER M 206 −1.651 −23.006 16.468 1.00 0.00O ATOM 550 N LEU M 207 −0.143 −23.008 19.874 1.00 0.00 N ATOM 551 CA LEUM 207 0.392 −21.871 20.615 1.00 0.00 C ATOM 552 C LEU M 207 1.815−22.188 21.070 1.00 0.00 C ATOM 553 O LEU M 207 2.709 −21.379 20.8641.00 0.00 O ATOM 554 CB LEU M 207 −0.487 −21.463 21.816 1.00 0.00 C ATOM555 CG LEU M 207 −1.681 −20.526 21.513 1.00 0.00 C ATOM 556 CD1 LEU M207 −1.223 −19.102 21.205 1.00 0.00 C ATOM 557 CD2 LEU M 207 −2.610−21.034 20.412 1.00 0.00 C ATOM 558 N SER M 208 1.997 −23.392 21.7481.00 0.00 N ATOM 559 CA SER M 208 3.280 −23.736 22.372 1.00 0.00 C ATOM560 C SER M 208 4.455 −23.617 21.403 1.00 0.00 C ATOM 561 O SER M 2085.522 −23.154 21.783 1.00 0.00 O ATOM 562 CB SER M 208 3.290 −25.11823.033 1.00 0.00 C ATOM 563 OG SER M 208 3.107 −26.159 22.078 1.00 0.00O ATOM 564 N LEU M 209 4.216 −24.105 20.122 1.00 0.00 N ATOM 565 CA LEUM 209 5.240 −24.173 19.081 1.00 0.00 C ATOM 566 C LEU M 209 6.054−22.878 19.001 1.00 0.00 C ATOM 567 O LEU M 209 7.275 −22.927 18.9191.00 0.00 O ATOM 568 CB LEU M 209 4.615 −24.547 17.722 1.00 0.00 C ATOM569 CG LEU M 209 5.609 −24.789 16.570 1.00 0.00 C ATOM 570 CD1 LEU M 2096.590 −25.923 16.871 1.00 0.00 C ATOM 571 CD2 LEU M 209 4.831 −25.11615.295 1.00 0.00 C ATOM 572 N ARG M 210 5.314 −21.695 19.000 1.00 0.00 NATOM 573 CA ARG M 210 5.938 −20.386 18.796 1.00 0.00 C ATOM 574 C ARG M210 7.094 −20.160 19.780 1.00 0.00 C ATOM 575 O ARG M 210 8.194 −19.78819.390 1.00 0.00 O ATOM 576 CB ARG M 210 4.919 −19.217 18.766 1.00 0.00C ATOM 577 CG ARG M 210 4.539 −18.617 20.123 1.00 0.00 C ATOM 578 CD ARGM 210 3.368 −17.645 20.037 1.00 0.00 C ATOM 579 NE ARG M 210 3.204−16.963 21.336 1.00 0.00 N ATOM 580 CZ ARG M 210 2.675 −17.521 22.4781.00 0.00 C ATOM 581 NH1 ARG M 210 2.108 −18.771 22.534 1.00 0.00 N ATOM582 NH2 ARG M 210 2.702 −16.823 23.658 1.00 0.00 N ATOM 583 N LEU M 2116.766 −20.348 21.118 1.00 0.00 N ATOM 584 CA LEU M 211 7.668 −19.97022.201 1.00 0.00 C ATOM 585 C LEU M 211 8.744 −21.017 22.457 1.00 0.00 CATOM 586 O LEU M 211 9.830 −20.675 22.903 1.00 0.00 O ATOM 587 CB LEU M211 6.921 −19.556 23.477 1.00 0.00 C ATOM 588 CG LEU M 211 6.253 −20.69124.283 1.00 0.00 C ATOM 589 CD1 LEU M 211 7.071 −21.031 25.529 1.00 0.00C ATOM 590 CD2 LEU M 211 4.828 −20.304 24.668 1.00 0.00 C ATOM 591 N PHEM 212 8.395 −22.335 22.194 1.00 0.00 N ATOM 592 CA PHE M 212 9.343−23.437 22.323 1.00 0.00 C ATOM 593 C PHE M 212 10.537 −23.177 21.4001.00 0.00 C ATOM 594 O PHE M 212 11.684 −23.308 21.810 1.00 0.00 O ATOM595 CB PHE M 212 8.657 −24.790 22.053 1.00 0.00 C ATOM 596 CG PHE M 2129.531 −26.001 22.266 1.00 0.00 C ATOM 597 CD1 PHE M 212 9.585 −27.01521.279 1.00 0.00 C ATOM 598 CD2 PHE M 212 10.273 −26.176 23.463 1.000.00 C ATOM 599 CE1 PHE M 212 10.360 −28.171 21.483 1.00 0.00 C ATOM 600CE2 PHE M 212 11.054 −27.328 23.659 1.00 0.00 C ATOM 601 CZ PHE M 21211.095 −28.324 22.671 1.00 0.00 C ATOM 602 N GLY M 213 10.213 −22.78220.106 1.00 0.00 N ATOM 603 CA GLY M 213 11.222 −22.358 19.149 1.00 0.00C ATOM 604 C GLY M 213 12.077 −21.244 19.726 1.00 0.00 C ATOM 605 O GLYM 213 13.296 −21.353 19.773 1.00 0.00 O ATOM 606 N ASN M 214 11.360−20.130 20.149 1.00 0.00 N ATOM 607 CA ASN M 214 12.007 −18.898 20.6041.00 0.00 C ATOM 608 C ASN M 214 13.063 −19.144 21.674 1.00 0.00 C ATOM609 O ASN M 214 14.176 −18.654 21.546 1.00 0.00 O ATOM 610 CB ASN M 21411.001 −17.841 21.083 1.00 0.00 C ATOM 611 CG ASN M 214 11.704 −16.60621.615 1.00 0.00 C ATOM 612 OD1 ASN M 214 11.859 −16.419 22.813 1.000.00 O ATOM 613 ND2 ASN M 214 12.177 −15.754 20.643 1.00 0.00 N ATOM 614N GLN M 252 6.092 −15.258 27.574 1.00 0.00 N ATOM 615 CA GLN M 252 5.399−15.988 26.508 1.00 0.00 C ATOM 616 C GLN M 252 4.487 −17.062 27.1091.00 0.00 C ATOM 617 O GLN M 252 3.343 −17.209 26.701 1.00 0.00 O ATOM618 CB GLN M 252 6.348 −16.641 25.488 1.00 0.00 C ATOM 619 CG GLN M 2527.165 −15.662 24.639 1.00 0.00 C ATOM 620 CD GLN M 252 6.294 −14.81223.745 1.00 0.00 C ATOM 621 OE1 GLN M 252 5.949 −13.685 24.069 1.00 0.00O ATOM 622 NE2 GLN M 252 5.911 −15.431 22.578 1.00 0.00 N ATOM 623 N ILEM 255 1.315 −15.654 28.673 1.00 0.00 N ATOM 624 CA ILE M 255 0.314−15.323 27.648 1.00 0.00 C ATOM 625 C ILE M 255 −0.456 −16.594 27.2701.00 0.00 C ATOM 626 O ILE M 255 −1.677 −16.562 27.206 1.00 0.00 O ATOM627 CB ILE M 255 0.899 −14.600 26.397 1.00 0.00 C ATOM 628 CG1 ILE M 2551.511 −13.217 26.721 1.00 0.00 C ATOM 629 CG2 ILE M 255 −0.132 −14.46225.269 1.00 0.00 C ATOM 630 CD1 ILE M 255 0.539 −12.178 27.265 1.00 0.00C ATOM 631 N PHE M 256 0.309 −17.724 26.987 1.00 0.00 N ATOM 632 CA PHEM 256 −0.300 −19.014 26.640 1.00 0.00 C ATOM 633 C PHE M 256 −1.370−19.377 27.673 1.00 0.00 C ATOM 634 O PHE M 256 −2.501 −19.676 27.3091.00 0.00 O ATOM 635 CB PHE M 256 0.741 −20.143 26.468 1.00 0.00 C ATOM636 CG PHE M 256 0.139 −21.530 26.434 1.00 0.00 C ATOM 637 CD1 PHE M 2560.410 −22.456 27.472 1.00 0.00 C ATOM 638 CD2 PHE M 256 −0.735 −21.92025.391 1.00 0.00 C ATOM 639 CE1 PHE M 256 −0.169 −23.740 27.459 1.000.00 C ATOM 640 CE2 PHE M 256 −1.314 −23.203 25.379 1.00 0.00 C ATOM 641CZ PHE M 256 −1.029 −24.114 26.412 1.00 0.00 C ATOM 642 N LEU M 259−4.533 −17.251 27.581 1.00 0.00 N ATOM 643 CA LEU M 259 −5.286 −17.37026.332 1.00 0.00 C ATOM 644 C LEU M 259 −6.190 −18.597 26.384 1.00 0.00C ATOM 645 O LEU M 259 −7.382 −18.501 26.120 1.00 0.00 O ATOM 646 CB LEUM 259 −4.356 −17.357 25.099 1.00 0.00 C ATOM 647 CG LEU M 259 −5.088−17.225 23.745 1.00 0.00 C ATOM 648 CD1 LEU M 259 −4.218 −16.458 22.7491.00 0.00 C ATOM 649 CD2 LEU M 259 −5.448 −18.586 23.146 1.00 0.00 C

TABLE 5 ATOM 1 N ALA A 21 5.881 −12.842 −1.403 1.00 0.00 N ATOM 2 CA ALAA 21 5.032 −12.962 −0.219 1.00 0.00 C ATOM 3 C ALA A 21 3.724 −12.190−0.393 1.00 0.00 C ATOM 4 O ALA A 21 2.644 −12.753 −0.261 1.00 0.00 OATOM 5 CB ALA A 21 5.743 −12.524 1.061 1.00 0.00 C ATOM 6 N ILE A 223.865 −10.830 −0.654 1.00 0.00 N ATOM 7 CA ILE A 22 2.696 −9.942 −0.7071.00 0.00 C ATOM 8 C ILE A 22 1.780 −10.304 −1.877 1.00 0.00 C ATOM 9 OILE A 22 0.564 −10.249 −1.742 1.00 0.00 O ATOM 10 CB ILE A 22 3.012−8.420 −0.634 1.00 0.00 C ATOM 11 CG1 ILE A 22 3.808 −7.845 −1.829 1.000.00 C ATOM 12 CG2 ILE A 22 3.732 −8.094 0.679 1.00 0.00 C ATOM 13 CD1ILE A 22 2.917 −7.216 −2.890 1.00 0.00 C ATOM 14 N ALA A 24 1.317−13.263 −3.458 1.00 0.00 N ATOM 15 CA ALA A 24 0.563 −14.470 −3.134 1.000.00 C ATOM 16 C ALA A 24 −0.656 −14.135 −2.280 1.00 0.00 C ATOM 17 OALA A 24 −1.754 −14.581 −2.580 1.00 0.00 O ATOM 18 CB ALA A 24 1.423−15.525 −2.443 1.00 0.00 C ATOM 19 N GLY A 25 −0.414 −13.331 −1.171 1.000.00 N ATOM 20 CA GLY A 25 −1.450 −12.972 −0.212 1.00 0.00 C ATOM 21 CGLY A 25 −2.689 −12.390 −0.872 1.00 0.00 C ATOM 22 O GLY A 25 −3.799−12.857 −0.647 1.00 0.00 O ATOM 23 N LEU A 59 −1.069 −19.335 −3.710 1.000.00 N ATOM 24 CA LEU A 59 −0.138 −19.537 −2.599 1.00 0.00 C ATOM 25 CLEU A 59 1.257 −19.890 −3.118 1.00 0.00 C ATOM 26 O LEU A 59 2.236−19.287 −2.700 1.00 0.00 O ATOM 27 CB LEU A 59 −0.654 −20.593 −1.5991.00 0.00 C ATOM 28 CG LEU A 59 0.253 −20.834 −0.375 1.00 0.00 C ATOM 29CD1 LEU A 59 0.412 −19.583 0.489 1.00 0.00 C ATOM 30 CD2 LEU A 59 −0.317−21.972 0.469 1.00 0.00 C ATOM 31 N ILE K 16 10.647 −2.985 11.484 1.000.00 N ATOM 32 CA ILE K 16 9.949 −4.131 12.078 1.00 0.00 C ATOM 33 C ILEK 16 8.633 −3.639 12.688 1.00 0.00 C ATOM 34 O ILE K 16 7.578 −4.19212.405 1.00 0.00 O ATOM 35 CB ILE K 16 10.839 −4.911 13.092 1.00 0.00 CATOM 36 CG1 ILE K 16 11.982 −5.650 12.360 1.00 0.00 C ATOM 37 CG2 ILE K16 10.028 −5.918 13.915 1.00 0.00 C ATOM 38 CD1 ILE K 16 13.158 −5.96113.274 1.00 0.00 C ATOM 39 N GLY K 19 5.970 −2.022 10.048 1.00 0.00 NATOM 40 CA GLY K 19 5.412 −3.072 9.210 1.00 0.00 C ATOM 41 C GLY K 194.400 −3.910 9.967 1.00 0.00 C ATOM 42 O GLY K 19 3.291 −4.135 9.4981.00 0.00 O ATOM 43 N GLY K 20 4.855 −4.394 11.185 1.00 0.00 N ATOM 44CA GLY K 20 4.029 −5.189 12.076 1.00 0.00 C ATOM 45 C GLY K 20 2.705−4.513 12.381 1.00 0.00 C ATOM 46 O GLY K 20 1.655 −5.133 12.286 1.000.00 O ATOM 47 N ALA K 21 2.813 −3.195 12.802 1.00 0.00 N ATOM 48 CA ALAK 21 1.674 −2.403 13.259 1.00 0.00 C ATOM 49 C ALA K 21 0.573 −2.35812.210 1.00 0.00 C ATOM 50 O ALA K 21 −0.571 −2.687 12.496 1.00 0.00 OATOM 51 CB ALA K 21 2.069 −0.980 13.646 1.00 0.00 C ATOM 52 N ILE K 220.959 −1.866 10.968 1.00 0.00 N ATOM 53 CA ILE K 22 −0.022 −1.644 9.9021.00 0.00 C ATOM 54 C ILE K 22 −0.648 −2.967 9.462 1.00 0.00 C ATOM 55 OILE K 22 −1.839 −3.017 9.187 1.00 0.00 O ATOM 56 CB ILE K 22 0.471−0.759 8.721 1.00 0.00 C ATOM 57 CG1 ILE K 22 1.645 −1.331 7.895 1.000.00 C ATOM 58 CG2 ILE K 22 0.838 0.636 9.238 1.00 0.00 C ATOM 59 CD1ILE K 22 1.196 −2.128 6.680 1.00 0.00 C ATOM 60 N GLY K 23 0.209 −4.0609.392 1.00 0.00 N ATOM 61 CA GLY K 23 −0.252 −5.389 9.028 1.00 0.00 CATOM 62 C GLY K 23 −1.370 −5.851 9.940 1.00 0.00 C ATOM 63 O GLY K 23−2.445 −6.210 9.480 1.00 0.00 O ATOM 64 N ALA K 24 −1.045 −5.828 11.2901.00 0.00 N ATOM 65 CA ALA K 24 −1.970 −6.229 12.347 1.00 0.00 C ATOM 66C ALA K 24 −3.298 −5.486 12.227 1.00 0.00 C ATOM 67 O ALA K 24 −4.355−6.101 12.268 1.00 0.00 O ATOM 68 CB ALA K 24 −1.374 −6.022 13.737 1.000.00 C ATOM 69 N GLY K 25 −3.201 −4.105 12.103 1.00 0.00 N ATOM 70 CAGLY K 25 −4.358 −3.224 12.066 1.00 0.00 C ATOM 71 C GLY K 25 −5.345−3.604 10.977 1.00 0.00 C ATOM 72 O GLY K 25 −6.530 −3.776 11.233 1.000.00 O ATOM 73 N GLY K 27 −5.390 −6.420 9.296 1.00 0.00 N ATOM 74 CA GLYK 27 −5.822 −7.781 9.578 1.00 0.00 C ATOM 75 C GLY K 27 −7.102 −7.83110.391 1.00 0.00 C ATOM 76 O GLY K 27 −8.060 −8.484 9.997 1.00 0.00 OATOM 77 N ASP K 28 −7.068 −7.107 11.579 1.00 0.00 N ATOM 78 CA ASP K 28−8.213 −7.027 12.494 1.00 0.00 C ATOM 79 C ASP K 28 −9.473 −6.650 11.7281.00 0.00 C ATOM 80 O ASP K 28 −10.504 −7.289 11.892 1.00 0.00 O ATOM 81CB ASP K 28 −8.029 −6.024 13.647 1.00 0.00 C ATOM 82 CG ASP K 28 −7.176−6.602 14.743 1.00 0.00 C ATOM 83 OD1 ASP K 28 −5.961 −6.498 14.817 1.000.00 O ATOM 84 OD2 ASP K 28 −7.934 −7.314 15.613 1.00 0.00 O ATOM 85 NALA K 31 −10.360 −9.341 8.254 1.00 0.00 N ATOM 86 CA ALA K 31 −10.595−10.710 8.645 1.00 0.00 C ATOM 87 C ALA K 31 −11.886 −10.733 9.598 1.000.00 C ATOM 88 O ALA K 31 −12.791 −11.543 9.438 1.00 0.00 O ATOM 89 CBALA K 31 −9.513 −11.450 9.262 1.00 0.00 C ATOM 90 N PHE K 53 −11.251−14.828 19.330 1.00 0.00 N ATOM 91 CA PHE K 53 −10.086 −15.010 18.9101.00 0.00 C ATOM 92 C PHE K 53 −9.416 −14.919 17.715 1.00 0.00 C ATOM 93O PHE K 53 −8.214 −14.687 17.727 1.00 0.00 O ATOM 94 CB PHE K 53 −10.413−17.088 18.615 1.00 0.00 C ATOM 95 CG PHE K 53 −9.168 −17.944 18.6561.00 0.00 C ATOM 96 CD1 PHE K 53 −8.363 −18.116 17.502 1.00 0.00 C ATOM97 CD2 PHE K 53 −8.769 −18.572 19.864 1.00 0.00 C ATOM 98 CE1 PHE K 53−7.177 −18.871 17.564 1.00 0.00 C ATOM 99 CE2 PHE K 53 −7.587 −19.33519.920 1.00 0.00 C ATOM 100 CZ PHE K 53 −6.787 −19.478 18.772 1.00 0.00C ATOM 101 N PHE K 54 −10.253 −14.602 16.650 1.00 0.00 N ATOM 102 CA PHEK 54 −9.754 −13.946 15.437 1.00 0.00 C ATOM 103 C PHE K 54 −9.027−12.653 15.816 1.00 0.00 C ATOM 104 O PHE K 54 −7.868 −12.465 15.4691.00 0.00 O ATOM 105 CB PHE K 54 −10.857 −13.644 14.396 1.00 0.00 C ATOM106 CG PHE K 54 −11.031 −14.732 13.363 1.00 0.00 C ATOM 107 CD1 PHE K 54−10.657 −14.497 12.014 1.00 0.00 C ATOM 108 CD2 PHE K 54 −11.600 −15.98613.699 1.00 0.00 C ATOM 109 CE1 PHE K 54 −10.855 −15.483 11.030 1.000.00 C ATOM 110 CE2 PHE K 54 −11.796 −16.971 12.711 1.00 0.00 C ATOM 111CZ PHE K 54 −11.427 −16.719 11.377 1.00 0.00 C ATOM 112 N ILE K 55−9.789 −11.720 16.511 1.00 0.00 N ATOM 113 CA ILE K 55 −9.296 −10.35916.735 1.00 0.00 C ATOM 114 C ILE K 55 −8.075 −10.305 17.655 1.00 0.00 CATOM 115 O ILE K 55 −7.239 −9.431 17.475 1.00 0.00 O ATOM 116 CB ILE K55 −10.374 −9.314 17.141 1.00 0.00 C ATOM 117 CG1 ILE K 55 −11.066−9.614 18.484 1.00 0.00 C ATOM 118 CG2 ILE K 55 −11.397 −9.148 16.0111.00 0.00 C ATOM 119 CD1 ILE K 55 −11.876 −8.446 19.024 1.00 0.00 C ATOM120 N THR K 56 −8.005 −11.228 18.695 1.00 0.00 N ATOM 121 CA THR K 56−6.877 −11.241 19.628 1.00 0.00 C ATOM 122 C THR K 56 −5.591 −11.65318.909 1.00 0.00 C ATOM 123 O THR K 56 −4.545 −11.076 19.169 1.00 0.00 OATOM 124 CB THR K 56 −7.142 −12.025 20.940 1.00 0.00 C ATOM 125 OG1 THRK 56 −6.232 −11.582 21.949 1.00 0.00 O ATOM 126 CG2 THR K 56 −6.997−13.539 20.848 1.00 0.00 C ATOM 127 N VAL K 57 −5.684 −12.700 17.9931.00 0.00 N ATOM 128 CA VAL K 57 −4.525 −13.128 17.197 1.00 0.00 C ATOM129 C VAL K 57 −4.015 −11.905 16.430 1.00 0.00 C ATOM 130 O VAL K 57−2.835 −11.585 16.495 1.00 0.00 O ATOM 131 CB VAL K 57 −4.821 −14.34616.278 1.00 0.00 C ATOM 132 CG1 VAL K 57 −3.708 −14.594 15.256 1.00 0.00C ATOM 133 CG2 VAL K 57 −5.001 −15.618 17.111 1.00 0.00 C ATOM 134 N GLYK 58 −4.974 −11.224 15.688 1.00 0.00 N ATOM 135 CA GLY K 58 −4.665−10.040 14.902 1.00 0.00 C ATOM 136 C GLY K 58 −3.915 −8.999 15.716 1.000.00 C ATOM 137 O GLY K 58 −2.837 −8.566 15.338 1.00 0.00 O ATOM 138 NLEU K 59 −4.569 −8.588 16.866 1.00 0.00 N ATOM 139 CA LEU K 59 −4.102−7.488 17.709 1.00 0.00 C ATOM 140 C LEU K 59 −2.696 −7.785 18.219 1.000.00 C ATOM 141 O LEU K 59 −1.786 −6.994 18.011 1.00 0.00 O ATOM 142 CBLEU K 59 −5.084 −7.200 18.866 1.00 0.00 C ATOM 143 CG LEU K 59 −4.667−6.055 19.810 1.00 0.00 C ATOM 144 CD1 LEU K 59 −4.617 −4.705 19.0941.00 0.00 C ATOM 145 CD2 LEU K 59 −5.640 −5.983 20.985 1.00 0.00 C ATOM146 N VAL K 60 −2.575 −8.958 18.956 1.00 0.00 N ATOM 147 CA VAL K 60−1.376 −9.313 19.723 1.00 0.00 C ATOM 148 C VAL K 60 −0.172 −9.62118.808 1.00 0.00 C ATOM 149 O VAL K 60 0.965 −9.587 19.262 1.00 0.00 OATOM 150 CB VAL K 60 −1.666 −10.425 20.774 1.00 0.00 C ATOM 151 CG1 VALK 60 −0.436 −10.797 21.603 1.00 0.00 C ATOM 152 CG2 VAL K 60 −2.756−9.980 21.761 1.00 0.00 C ATOM 153 N GLU K 61 −0.439 −9.875 17.464 1.000.00 N ATOM 154 CA GLU K 61 0.617 −9.928 16.448 1.00 0.00 C ATOM 155 CGLU K 61 1.600 −8.765 16.629 1.00 0.00 C ATOM 156 O GLU K 61 2.806−8.976 16.643 1.00 0.00 O ATOM 157 CB GLU K 61 0.048 −9.957 15.018 1.000.00 C ATOM 158 CG GLU K 61 1.116 −10.204 13.955 1.00 0.00 C ATOM 159 CDGLU K 61 0.480 −10.239 12.589 1.00 0.00 C ATOM 160 OE1 GLU K 61 0.270−9.258 11.891 1.00 0.00 O ATOM 161 OE2 GLU K 61 0.106 −11.500 12.2551.00 0.00 O ATOM 162 N ALA K 62 1.026 −7.499 16.735 1.00 0.00 N ATOM 163CA ALA K 62 1.838 −6.288 16.832 1.00 0.00 C ATOM 164 C ALA K 62 2.817−6.381 18.011 1.00 0.00 C ATOM 165 O ALA K 62 4.014 −6.325 17.766 1.000.00 O ATOM 166 CB ALA K 62 1.026 −4.994 16.802 1.00 0.00 C ATOM 167 NTYR K 64 4.143 −8.947 19.533 1.00 0.00 N ATOM 168 CA TYR K 64 5.238−9.901 19.299 1.00 0.00 C ATOM 169 C TYR K 64 6.411 −9.187 18.617 1.000.00 C ATOM 170 O TYR K 64 7.549 −9.293 19.057 1.00 0.00 O ATOM 171 CBTYR K 64 4.859 −11.158 18.485 1.00 0.00 C ATOM 172 CG TYR K 64 3.743−12.009 19.045 1.00 0.00 C ATOM 173 CD1 TYR K 64 3.591 −12.248 20.4361.00 0.00 C ATOM 174 CD2 TYR K 64 2.826 −12.617 18.151 1.00 0.00 C ATOM175 CE1 TYR K 64 2.524 −13.026 20.919 1.00 0.00 C ATOM 176 CE2 TYR K 641.754 −13.394 18.625 1.00 0.00 C ATOM 177 CZ TYR K 64 1.603 −13.58220.014 1.00 0.00 C ATOM 178 OH TYR K 64 0.533 −14.296 20.528 1.00 0.00 OATOM 179 N PHE K 65 6.092 −8.473 17.468 1.00 0.00 N ATOM 180 CA PHE K 657.112 −7.764 16.688 1.00 0.00 C ATOM 181 C PHE K 65 7.701 −6.560 17.4231.00 0.00 C ATOM 182 O PHE K 65 8.869 −6.250 17.232 1.00 0.00 O ATOM 183CB PHE K 65 6.605 −7.346 15.295 1.00 0.00 C ATOM 184 CG PHE K 65 6.399−8.550 14.405 1.00 0.00 C ATOM 185 CD1 PHE K 65 7.512 −9.293 13.931 1.000.00 C ATOM 186 CE1 PHE K 65 7.321 −10.463 13.174 1.00 0.00 C ATOM 187CZ PHE K 65 6.021 −10.897 12.868 1.00 0.00 C ATOM 188 CE2 PHE K 65 4.911−10.153 13.301 1.00 0.00 C ATOM 189 CD2 PHE K 65 5.096 −8.983 14.0611.00 0.00 C ATOM 190 N ILE K 66 6.849 −5.852 18.262 1.00 0.00 N ATOM 191CA ILE K 66 7.323 −4.737 19.093 1.00 0.00 C ATOM 192 C ILE K 66 8.436−5.275 19.995 1.00 0.00 C ATOM 193 O ILE K 66 9.510 −4.692 20.045 1.000.00 O ATOM 194 CB ILE K 66 6.205 −4.010 19.896 1.00 0.00 C ATOM 195 CG1ILE K 66 5.194 −3.331 18.944 1.00 0.00 C ATOM 196 CG2 ILE K 66 6.795−2.959 20.847 1.00 0.00 C ATOM 197 CD1 ILE K 66 3.915 −2.888 19.641 1.000.00 C ATOM 198 N ASN K 67 8.135 −6.412 20.737 1.00 0.00 N ATOM 199 CAASN K 67 9.101 −7.043 21.643 1.00 0.00 C ATOM 200 C ASN K 67 10.396−7.398 20.922 1.00 0.00 C ATOM 201 O ASN K 67 11.470 −7.186 21.466 1.000.00 O ATOM 202 CB ASN K 67 8.561 −8.295 22.359 1.00 0.00 C ATOM 203 CGASN K 67 7.789 −7.913 23.607 1.00 0.00 C ATOM 204 OD1 ASN K 67 6.585−7.703 23.596 1.00 0.00 O ATOM 205 ND2 ASN K 67 8.574 −7.784 24.731 1.000.00 N ATOM 206 N LEU K 68 10.265 −8.000 19.676 1.00 0.00 N ATOM 207 CALEU K 68 11.425 −8.412 18.874 1.00 0.00 C ATOM 208 C LEU K 68 12.356−7.211 18.673 1.00 0.00 C ATOM 209 O LEU K 68 13.544 −7.283 18.962 1.000.00 O ATOM 210 CB LEU K 68 11.000 −9.085 17.550 1.00 0.00 C ATOM 211 CGLEU K 68 12.106 −9.924 16.872 1.00 0.00 C ATOM 212 CD1 LEU K 68 11.478−11.029 16.022 1.00 0.00 C ATOM 213 CD2 LEU K 68 13.020 −9.082 15.9831.00 0.00 C ATOM 214 N GLY L 14 15.198 −8.074 9.311 1.00 0.00 N ATOM 215CA GLY L 14 14.066 −7.197 9.559 1.00 0.00 C ATOM 216 C GLY L 14 12.995−7.318 8.489 1.00 0.00 C ATOM 217 O GLY L 14 11.827 −7.504 8.800 1.000.00 O ATOM 218 N ILE L 16 12.564 −9.668 6.039 1.00 0.00 N ATOM 219 CAILE L 16 11.972 −10.997 5.849 1.00 0.00 C ATOM 220 C ILE L 16 10.872−11.230 6.896 1.00 0.00 C ATOM 221 O ILE L 16 9.821 −11.769 6.579 1.000.00 O ATOM 222 CB ILE L 16 13.034 −12.140 5.737 1.00 0.00 C ATOM 223CG1 ILE L 16 12.723 −13.142 4.605 1.00 0.00 C ATOM 224 CG2 ILE L 1613.344 −12.873 7.046 1.00 0.00 C ATOM 225 CD1 ILE L 16 11.458 −13.9714.775 1.00 0.00 C ATOM 226 N MET L 17 11.163 −10.818 8.193 1.00 0.00 NATOM 227 CA MET L 17 10.196 −10.952 9.281 1.00 0.00 C ATOM 228 C MET L17 8.956 −10.129 8.951 1.00 0.00 C ATOM 229 O MET L 17 7.865 −10.6758.862 1.00 0.00 O ATOM 230 CB MET L 17 10.759 −10.564 10.663 1.00 0.00 CATOM 231 CG MET L 17 11.766 −11.566 11.230 1.00 0.00 C ATOM 232 SD MET L17 10.949 −13.111 11.753 1.00 0.00 S ATOM 233 CE MET L 17 11.549 −14.21610.448 1.00 0.00 C ATOM 234 N ALA L 18 9.158 −8.765 8.795 1.00 0.00 NATOM 235 CA ALA L 18 8.046 −7.822 8.702 1.00 0.00 C ATOM 236 C ALA L 187.152 −8.180 7.521 1.00 0.00 C ATOM 237 O ALA L 18 5.975 −8.477 7.6921.00 0.00 O ATOM 238 CB ALA L 18 8.510 −6.370 8.625 1.00 0.00 C ATOM 239N GLY L 19 7.766 −8.127 6.279 1.00 0.00 N ATOM 240 CA GLY L 19 7.039−8.324 5.037 1.00 0.00 C ATOM 241 C GLY L 19 6.426 −9.707 4.980 1.000.00 C ATOM 242 O GLY L 19 5.227 −9.857 4.788 1.00 0.00 O ATOM 243 N GLYL 20 7.342 −10.737 5.121 1.00 0.00 N ATOM 244 CA GLY L 20 7.000 −12.1314.906 1.00 0.00 C ATOM 245 C GLY L 20 5.877 −12.608 5.802 1.00 0.00 CATOM 246 O GLY L 20 4.881 −13.136 5.327 1.00 0.00 O ATOM 247 N ALA L 216.105 −12.439 7.161 1.00 0.00 N ATOM 248 CA ALA L 21 5.177 −12.957 8.1671.00 0.00 C ATOM 249 C ALA L 21 3.795 −12.317 8.072 1.00 0.00 C ATOM 250O ALA L 21 2.795 −12.996 8.255 1.00 0.00 O ATOM 251 CB ALA L 21 5.700−12.806 9.589 1.00 0.00 C ATOM 252 N ILE L 22 3.756 −10.947 7.836 1.000.00 N ATOM 253 CA ILE L 22 2.476 −10.243 7.663 1.00 0.00 C ATOM 254 CILE L 22 1.766 −10.786 6.419 1.00 0.00 C ATOM 255 O ILE L 22 0.554−10.946 6.440 1.00 0.00 O ATOM 256 CB ILE L 22 2.626 −8.694 7.709 1.000.00 C ATOM 257 CG1 ILE L 22 2.574 −8.158 9.161 1.00 0.00 C ATOM 258 CG2ILE L 22 1.550 −7.959 6.902 1.00 0.00 C ATOM 259 CD1 ILE L 22 3.547−8.791 10.144 1.00 0.00 C ATOM 260 N GLY L 23 2.556 −11.065 5.313 1.000.00 N ATOM 261 CA GLY L 23 2.039 −11.727 4.122 1.00 0.00 C ATOM 262 CGLY L 23 1.274 −12.998 4.463 1.00 0.00 C ATOM 263 O GLY L 23 0.151−13.189 4.016 1.00 0.00 O ATOM 264 N ALA L 24 1.957 −13.889 5.281 1.000.00 N ATOM 265 CA ALA L 24 1.364 −15.139 5.762 1.00 0.00 C ATOM 266 CALA L 24 0.049 −14.890 6.499 1.00 0.00 C ATOM 267 O ALA L 24 −0.925−15.594 6.275 1.00 0.00 O ATOM 268 CB ALA L 24 2.317 −15.935 6.650 1.000.00 C ATOM 269 N GLY L 25 0.070 −13.864 7.434 1.00 0.00 N ATOM 270 CAGLY L 25 −1.089 −13.467 8.219 1.00 0.00 C ATOM 271 C GLY L 25 −2.292−13.111 7.362 1.00 0.00 C ATOM 272 O GLY L 25 −3.397 −13.566 7.623 1.000.00 O ATOM 273 N ILE L 26 −2.031 −12.218 6.329 1.00 0.00 N ATOM 274 CAILE L 26 −3.054 −11.761 5.381 1.00 0.00 C ATOM 275 C ILE L 26 −3.674−13.003 4.743 1.00 0.00 C ATOM 276 O ILE L 26 −4.889 −13.145 4.749 1.000.00 O ATOM 277 CB ILE L 26 −2.514 −10.752 4.324 1.00 0.00 C ATOM 278CG1 ILE L 26 −2.147 −9.409 4.994 1.00 0.00 C ATOM 279 CG2 ILE L 26−3.535 −10.506 3.201 1.00 0.00 C ATOM 280 CD1 ILE L 26 −1.217 −8.5544.146 1.00 0.00 C ATOM 281 N GLY L 27 −2.774 −13.896 4.170 1.00 0.00 NATOM 282 CA GLY L 27 −3.181 −15.110 3.481 1.00 0.00 C ATOM 283 C GLY L27 −4.140 −15.936 4.316 1.00 0.00 C ATOM 284 O GLY L 27 −5.230 −16.2673.870 1.00 0.00 O ATOM 285 N ASP L 28 −3.663 −16.268 5.578 1.00 0.00 NATOM 286 CA ASP L 28 −4.426 −17.067 6.539 1.00 0.00 C ATOM 287 C ASP L28 −5.824 −16.490 6.730 1.00 0.00 C ATOM 288 O ASP L 28 −6.793 −17.2356.725 1.00 0.00 O ATOM 289 CB ASP L 28 −3.714 −17.205 7.894 1.00 0.00 CATOM 290 CG ASP L 28 −4.554 −17.995 8.870 1.00 0.00 C ATOM 291 OD1 ASP L28 −5.304 −17.502 9.701 1.00 0.00 O ATOM 292 OD2 ASP L 28 −4.426 −19.3318.666 1.00 0.00 O ATOM 293 N GLY L 29 −5.891 −15.120 6.948 1.00 0.00 NATOM 294 CA GLY L 29 −7.140 −14.419 7.187 1.00 0.00 C ATOM 295 C GLY L29 −8.116 −14.632 6.046 1.00 0.00 C ATOM 296 O GLY L 29 −9.157 −15.2516.219 1.00 0.00 O ATOM 297 N VAL L 30 −7.724 −14.059 4.844 1.00 0.00 NATOM 298 CA VAL L 30 −8.629 −13.949 3.692 1.00 0.00 C ATOM 299 C VAL L30 −9.094 −15.327 3.208 1.00 0.00 C ATOM 300 O VAL L 30 −10.279 −15.5432.987 1.00 0.00 O ATOM 301 CB VAL L 30 −8.106 −13.054 2.531 1.00 0.00 CATOM 302 CG1 VAL L 30 −7.924 −11.606 2.995 1.00 0.00 C ATOM 303 CG2 VALL 30 −6.817 −13.548 1.866 1.00 0.00 C ATOM 304 N ALA L 31 −8.091 −16.2723.023 1.00 0.00 N ATOM 305 CA ALA L 31 −8.388 −17.640 2.597 1.00 0.00 CATOM 306 C ALA L 31 −9.244 −18.351 3.642 1.00 0.00 C ATOM 307 O ALA L 31−10.141 −19.108 3.299 1.00 0.00 O ATOM 308 CB ALA L 31 −7.130 −18.4552.312 1.00 0.00 C ATOM 309 N GLY L 32 −8.904 −18.097 4.963 1.00 0.00 NATOM 310 CA GLY L 32 −9.633 −18.628 6.099 1.00 0.00 C ATOM 311 C GLY L32 −11.116 −18.323 6.071 1.00 0.00 C ATOM 312 O GLY L 32 −11.909 −19.1666.460 1.00 0.00 O ATOM 313 N PHE L 53 −8.496 −25.187 12.274 1.00 0.00 NATOM 314 CA PHE L 53 −8.171 −23.763 12.130 1.00 0.00 C ATOM 315 C PHE L53 −6.890 −23.457 12.911 1.00 0.00 C ATOM 316 O PHE L 53 −5.962 −22.86712.377 1.00 0.00 O ATOM 317 CB PHE L 53 −9.326 −22.816 12.515 1.00 0.00C ATOM 318 CG PHE L 53 −8.993 −21.357 12.292 1.00 0.00 C ATOM 319 CD1PHE L 53 −8.825 −20.842 10.980 1.00 0.00 C ATOM 320 CD2 PHE L 53 −8.839−20.476 13.391 1.00 0.00 C ATOM 321 CE1 PHE L 53 −8.485 −19.490 10.7791.00 0.00 C ATOM 322 CE2 PHE L 53 −8.500 −19.125 13.186 1.00 0.00 C ATOM323 CZ PHE L 53 −8.317 −18.634 11.882 1.00 0.00 C ATOM 324 N PHE L 54−6.879 −23.863 14.237 1.00 0.00 N ATOM 325 CA PHE L 54 −5.791 −23.48415.142 1.00 0.00 C ATOM 326 C PHE L 54 −4.446 −24.003 14.630 1.00 0.00 CATOM 327 O PHE L 54 −3.462 −23.274 14.628 1.00 0.00 O ATOM 328 CB PHE L54 −6.001 −23.941 16.598 1.00 0.00 C ATOM 329 CG PHE L 54 −7.288 −23.50017.265 1.00 0.00 C ATOM 330 CD1 PHE L 54 −7.981 −22.312 16.907 1.00 0.00C ATOM 331 CD2 PHE L 54 −7.828 −24.299 18.301 1.00 0.00 C ATOM 332 CE1PHE L 54 −9.188 −21.961 17.539 1.00 0.00 C ATOM 333 CE2 PHE L 54 −9.027−23.943 18.937 1.00 0.00 C ATOM 334 CZ PHE L 54 −9.708 −22.777 18.5571.00 0.00 C ATOM 335 N ILE L 55 −4.415 −25.339 14.241 1.00 0.00 N ATOM336 CA ILE L 55 −3.169 −25.944 13.764 1.00 0.00 C ATOM 337 C ILE L 55−2.708 −25.302 12.450 1.00 0.00 C ATOM 338 O ILE L 55 −1.515 −25.10312.267 1.00 0.00 O ATOM 339 CB ILE L 55 −3.180 −27.498 13.738 1.00 0.00C ATOM 340 CG1 ILE L 55 −1.738 −28.049 13.695 1.00 0.00 C ATOM 341 CG2ILE L 55 −4.026 −28.078 12.602 1.00 0.00 C ATOM 342 CD1 ILE L 55 −1.648−29.541 13.981 1.00 0.00 C ATOM 343 N THR L 56 −3.685 −25.022 11.4951.00 0.00 N ATOM 344 CA THR L 56 −3.324 −24.487 10.182 1.00 0.00 C ATOM345 C THR L 56 −2.776 −23.057 10.234 1.00 0.00 C ATOM 346 O THR L 56−2.032 −22.682 9.339 1.00 0.00 O ATOM 347 CB THR L 56 −4.411 −24.6769.094 1.00 0.00 C ATOM 348 OG1 THR L 56 −3.794 −24.763 7.805 1.00 0.00 OATOM 349 CG2 THR L 56 −5.482 −23.591 9.035 1.00 0.00 C ATOM 350 N VAL L57 −3.164 −22.246 11.299 1.00 0.00 N ATOM 351 CA VAL L 57 −2.504 −20.95511.560 1.00 0.00 C ATOM 352 C VAL L 57 −0.999 −21.238 11.646 1.00 0.00 CATOM 353 O VAL L 57 −0.210 −20.630 10.934 1.00 0.00 O ATOM 354 CB VAL L57 −3.046 −20.209 12.813 1.00 0.00 C ATOM 355 CG1 VAL L 57 −2.177−19.007 13.193 1.00 0.00 C ATOM 356 CG2 VAL L 57 −4.475 −19.712 12.5881.00 0.00 C ATOM 357 N GLY L 58 −0.638 −22.227 12.555 1.00 0.00 N ATOM358 CA GLY L 58 0.734 −22.669 12.735 1.00 0.00 C ATOM 359 C GLY L 581.405 −23.027 11.420 1.00 0.00 C ATOM 360 O GLY L 58 2.484 −22.53611.126 1.00 0.00 O ATOM 361 N LEU L 59 0.728 −23.952 10.636 1.00 0.00 NATOM 362 CA LEU L 59 1.280 −24.490 9.384 1.00 0.00 C ATOM 363 C LEU L 591.613 −23.390 8.370 1.00 0.00 C ATOM 364 O LEU L 59 2.651 −23.446 7.7251.00 0.00 O ATOM 365 CB LEU L 59 0.366 −25.532 8.706 1.00 0.00 C ATOM366 CG LEU L 59 0.194 −26.846 9.498 1.00 0.00 C ATOM 367 CD1 LEU L 59−0.918 −27.689 8.875 1.00 0.00 C ATOM 368 CD2 LEU L 59 1.486 −27.6639.541 1.00 0.00 C ATOM 369 N VAL L 60 0.655 −22.399 8.202 1.00 0.00 NATOM 370 CA VAL L 60 0.818 −21.290 7.253 1.00 0.00 C ATOM 371 C VAL L 602.049 −20.455 7.640 1.00 0.00 C ATOM 372 O VAL L 60 2.832 −20.078 6.7781.00 0.00 O ATOM 373 CB VAL L 60 −0.480 −20.445 7.107 1.00 0.00 C ATOM374 CG1 VAL L 60 −0.256 −19.131 6.358 1.00 0.00 C ATOM 375 CG2 VAL L 60−1.560 −21.237 6.361 1.00 0.00 C ATOM 376 N GLU L 61 2.172 −20.129 8.9861.00 0.00 N ATOM 377 CA GLU L 61 3.337 −19.405 9.510 1.00 0.00 C ATOM378 C GLU L 61 4.651 −20.199 9.436 1.00 0.00 C ATOM 379 O GLU L 61 5.716−19.596 9.419 1.00 0.00 O ATOM 380 CB GLU L 61 3.138 −18.941 10.962 1.000.00 C ATOM 381 CG GLU L 61 2.061 −17.864 11.090 1.00 0.00 C ATOM 382 CDGLU L 61 2.006 −17.374 12.535 1.00 0.00 C ATOM 383 OE1 GLU L 61 1.291−18.073 13.310 1.00 0.00 O ATOM 384 OE2 GLU L 61 2.715 −16.364 12.7861.00 0.00 O ATOM 385 N ALA L 62 4.558 −21.588 9.464 1.00 0.00 N ATOM 386CA ALA L 62 5.692 −22.469 9.740 1.00 0.00 C ATOM 387 C ALA L 62 6.978−22.140 8.986 1.00 0.00 C ATOM 388 O ALA L 62 8.021 −22.108 9.623 1.000.00 O ATOM 389 CB ALA L 62 5.366 −23.956 9.613 1.00 0.00 C ATOM 390 NTYR L 64 8.184 −19.301 7.912 1.00 0.00 N ATOM 391 CA TYR L 64 8.775−18.086 8.479 1.00 0.00 C ATOM 392 C TYR L 64 9.317 −18.325 9.892 1.000.00 C ATOM 393 O TYR L 64 10.332 −17.753 10.266 1.00 0.00 O ATOM 394 CBTYR L 64 7.803 −16.892 8.449 1.00 0.00 C ATOM 395 CG TYR L 64 7.396−16.567 7.028 1.00 0.00 C ATOM 396 CD1 TYR L 64 8.268 −15.834 6.184 1.000.00 C ATOM 397 CD2 TYR L 64 6.169 −17.040 6.496 1.00 0.00 C ATOM 398CE1 TYR L 64 7.935 −15.597 4.837 1.00 0.00 C ATOM 399 CE2 TYR L 64 5.833−16.808 5.148 1.00 0.00 C ATOM 400 CZ TYR L 64 6.713 −16.085 4.325 1.000.00 C ATOM 401 OH TYR L 64 6.340 −15.867 3.006 1.00 0.00 O ATOM 402 NPHE L 65 8.591 −19.196 10.695 1.00 0.00 N ATOM 403 CA PHE L 65 9.106−19.699 11.977 1.00 0.00 C ATOM 404 C PHE L 65 10.500 −20.313 11.7661.00 0.00 C ATOM 405 O PHE L 65 11.435 −19.983 12.486 1.00 0.00 O ATOM406 CB PHE L 65 8.086 −20.622 12.690 1.00 0.00 C ATOM 407 CG PHE L 658.660 −21.781 13.471 1.00 0.00 C ATOM 408 CD1 PHE L 65 9.445 −21.57014.632 1.00 0.00 C ATOM 409 CE1 PHE L 65 9.992 −22.664 15.330 1.00 0.00C ATOM 410 CZ PHE L 65 9.742 −23.979 14.897 1.00 0.00 C ATOM 411 CE2 PHEL 65 8.951 −24.200 13.758 1.00 0.00 C ATOM 412 CD2 PHE L 65 8.417−23.111 13.045 1.00 0.00 C ATOM 413 N ILE L 66 10.602 −21.255 10.7461.00 0.00 N ATOM 414 CA ILE L 66 11.863 −21.934 10.436 1.00 0.00 C ATOM415 C ILE L 66 12.921 −20.880 10.109 1.00 0.00 C ATOM 416 O ILE L 6614.024 −20.969 10.629 1.00 0.00 O ATOM 417 CB ILE L 66 11.743 −23.0279.333 1.00 0.00 C ATOM 418 CG1 ILE L 66 10.834 −24.206 9.754 1.00 0.00 CATOM 419 CG2 ILE L 66 13.112 −23.552 8.880 1.00 0.00 C ATOM 420 CD1 ILEL 66 11.332 −25.031 10.935 1.00 0.00 C ATOM 421 N ASN L 67 12.568−19.878 8.205 1.00 0.00 N ATOM 422 CA ASN L 67 13.514 −18.826 8.807 1.000.00 C ATOM 423 C ASN L 67 14.165 −18.202 10.035 1.00 0.00 C ATOM 424 OASN L 67 15.379 −18.068 10.066 1.00 0.00 O ATOM 425 CB ASN L 67 12.928−17.686 7.946 1.00 0.00 C ATOM 426 CG ASN L 67 12.679 −18.089 6.508 1.000.00 C ATOM 427 OD1 ASN L 67 11.560 −18.310 6.072 1.00 0.00 O ATOM 428ND2 ASN L 67 13.821 −18.186 5.747 1.00 0.00 N ATOM 429 N LEU L 68 13.303−17.783 11.044 1.00 0.00 N ATOM 430 CA LEU L 68 13.771 −17.078 12.2431.00 0.00 C ATOM 431 C LEU L 68 14.883 −17.907 12.894 1.00 0.00 C ATOM432 O LEU L 68 16.014 −17.453 13.016 1.00 0.00 O ATOM 433 CB LEU L 6812.610 −16.759 13.216 1.00 0.00 C ATOM 434 CG LEU L 68 12.886 −15.63814.239 1.00 0.00 C ATOM 435 CD1 LEU L 68 11.590 −15.292 14.973 1.00 0.00C ATOM 436 CD2 LEU L 68 13.950 −16.005 15.272 1.00 0.00 C ATOM 437 N ALAL 69 14.497 −19.171 13.327 1.00 0.00 N ATOM 438 CA ALA L 69 15.382−20.029 14.117 1.00 0.00 C ATOM 439 C ALA L 69 16.671 −20.348 13.3601.00 0.00 C ATOM 440 O ALA L 69 10.761 −20.262 13.911 1.00 0.00 O ATOM441 CB ALA L 69 14.694 −21.321 14.552 1.00 0.00 C ATOM 442 N PRO K 632.328 −6.569 19.314 1.00 0.00 N ATOM 443 CA PRO K 63 3.195 −6.836 20.4501.00 0.00 C ATOM 444 C PRO K 63 4.365 −7.788 20.267 1.00 0.00 C ATOM 445O PRO K 63 5.439 −7.509 20.781 1.00 0.00 O ATOM 446 CB PRO K 63 2.260−7.282 21.557 1.00 0.00 C ATOM 447 CG PRO K 63 0.996 −6.494 21.282 1.000.00 C ATOM 448 CD PRO K 63 0.991 −6.259 19.780 1.00 0.00 C ATOM 449 NPRO L 63 6.948 −21.920 7.602 1.00 0.00 N ATOM 450 CA PRO L 63 8.151−21.540 6.873 1.00 0.00 C ATOM 451 C PRO L 63 8.940 −20.389 7.501 1.000.00 C ATOM 452 O PRO L 63 10.158 −20.447 7.588 1.00 0.00 O ATOM 453 CBPRO L 63 7.683 −21.204 5.464 1.00 0.00 C ATOM 454 CG PRO L 63 6.402−21.994 5.304 1.00 0.00 C ATOM 455 CD PRO L 63 5.820 −22.071 6.701 1.000.00 C ATOM 456 N SER M 206 −1.465 −25.569 20.193 1.00 0.00 N ATOM 457CA SER M 206 −1.251 −24.467 19.250 1.00 0.00 C ATOM 458 C SER M 206−0.394 −23.364 19.890 1.00 0.00 C ATOM 459 O SER M 206 0.590 −22.92419.311 1.00 0.00 O ATOM 460 CB SER M 206 −2.578 −23.921 18.704 1.00 0.00C ATOM 461 OG SER M 206 −2.343 −22.955 17.679 1.00 0.00 O ATOM 462 N LEUM 207 −0.835 −22.896 21.123 1.00 0.00 N ATOM 463 CA LEU M 207 −0.188−21.775 21.816 1.00 0.00 C ATOM 464 C LEU M 207 1.276 −22.088 22.1451.00 0.00 C ATOM 465 O LEU M 207 2.137 −21.226 22.019 1.00 0.00 O ATOM466 CB LEU M 207 −0.942 −21.337 23.093 1.00 0.00 C ATOM 467 CG LEU M 207−2.049 −20.274 22.888 1.00 0.00 C ATOM 468 CD1 LEU M 207 −1.457 −18.89922.585 1.00 0.00 C ATOM 469 CD2 LEU M 207 −3.097 −20.644 21.838 1.000.00 C ATOM 470 N LEU M 209 3.398 −23.907 20.563 1.00 0.00 N ATOM 471 CALEU M 209 4.255 −23.926 19.376 1.00 0.00 C ATOM 472 C LEU M 209 5.088−22.645 19.269 1.00 0.00 C ATOM 473 O LEU M 209 6.295 −22.716 19.0781.00 0.00 O ATOM 474 CB LEU M 209 3.458 −24.190 18.082 1.00 0.00 C ATOM475 CG LEU M 209 4.307 −24.350 16.802 1.00 0.00 C ATOM 476 CD1 LEU M 2095.264 −25.541 16.875 1.00 0.00 C ATOM 477 CD2 LEU M 209 3.386 −24.50615.593 1.00 0.00 C ATOM 478 N ARG M 210 4.395 −21.436 19.334 1.00 0.00 NATOM 479 CA ARG M 210 5.121 −20.192 19.071 1.00 0.00 C ATOM 480 C ARG M210 6.175 −19.896 20.142 1.00 0.00 C ATOM 481 O ARG M 210 7.276 −19.47319.811 1.00 0.00 O ATOM 482 CB ARG M 210 4.268 −18.971 18.667 1.00 0.00C ATOM 483 CG ARG M 210 3.638 −18.112 19.768 1.00 0.00 C ATOM 484 CD ARGM 210 2.158 −18.393 20.003 1.00 0.00 C ATOM 485 NE ARG M 210 1.604−17.342 20.877 1.00 0.00 N ATOM 486 CZ ARG M 210 1.731 −17.257 22.2451.00 0.00 C ATOM 487 NH1 ARG M 210 2.289 −18.232 23.037 1.00 0.00 N ATOM488 NH2 ARG M 210 1.286 −16.136 22.899 1.00 0.00 N ATOM 489 N LEU M 2115.795 −20.083 21.471 1.00 0.00 N ATOM 490 CA LEU M 211 6.734 −19.80322.567 1.00 0.00 C ATOM 491 C LEU M 211 7.939 −20.746 22.556 1.00 0.00 CATOM 492 O LEU M 211 9.039 −20.338 22.899 1.00 0.00 O ATOM 493 CB LEU M211 6.067 −19.645 23.947 1.00 0.00 C ATOM 494 CG LEU M 211 5.526 −20.90924.642 1.00 0.00 C ATOM 495 CD1 LEU M 211 6.600 −21.602 25.484 1.00 0.00C ATOM 496 CD2 LEU M 211 4.341 −20.550 25.539 1.00 0.00 C ATOM 497 N PHEM 212 7.680 −22.052 22.157 1.00 0.00 N ATOM 498 CA PHE M 212 8.707−23.084 21.988 1.00 0.00 C ATOM 499 C PHE M 212 9.819 −22.550 21.0761.00 0.00 C ATOM 500 O PHE M 212 10.996 −22.649 21.401 1.00 0.00 O ATOM501 CB PHE M 212 8.068 −24.391 21.469 1.00 0.00 C ATOM 502 CG PHE M 2129.004 −25.542 21.220 1.00 0.00 C ATOM 503 CD1 PHE M 212 9.208 −26.02519.902 1.00 0.00 C ATOM 504 CD2 PHE M 212 9.628 −26.211 22.299 1.00 0.00C ATOM 505 CE1 PHE M 212 10.009 −27.158 19.672 1.00 0.00 C ATOM 506 CE2PHE M 212 10.431 −27.339 22.062 1.00 0.00 C ATOM 507 CZ PHE M 212 10.625−27.813 20.752 1.00 0.00 C ATOM 508 N GLY M 213 9.388 −21.965 19.8911.00 0.00 N ATOM 509 CA GLY M 213 10.301 −21.336 18.951 1.00 0.00 C ATOM510 C GLY M 213 11.123 −20.232 19.597 1.00 0.00 C ATOM 511 O GLY M 21312.347 −20.250 19.546 1.00 0.00 O ATOM 512 N ASN M 214 10.364 −19.22920.191 1.00 0.00 N ATOM 513 CA ASN M 214 10.951 −17.998 20.736 1.00 0.00C ATOM 514 C ASN M 214 12.113 −18.295 21.676 1.00 0.00 C ATOM 515 O ASNM 214 13.171 −17.697 21.543 1.00 0.00 O ATOM 516 CB ASN M 214 9.942−17.090 21.468 1.00 0.00 C ATOM 517 CG ASN M 214 9.292 −16.100 20.5221.00 0.00 C ATOM 518 OD1 ASN M 214 9.826 −15.042 20.224 1.00 0.00 O ATOM519 ND2 ASN M 214 8.080 −16.508 20.015 1.00 0.00 N ATOM 520 N GLN M 2525.809 −14.680 27.293 1.00 0.00 N ATOM 521 CA GLN M 252 4.947 −15.47526.417 1.00 0.00 C ATOM 522 C GLN M 252 3.965 −16.318 27.234 1.00 0.00 CATOM 523 O GLN M 252 2.796 −16.423 26.885 1.00 0.00 O ATOM 524 CB GLN M252 5.729 −16.384 25.460 1.00 0.00 C ATOM 525 CG GLN M 252 6.493 −15.63224.365 1.00 0.00 C ATOM 526 CD GLN M 252 5.558 −14.976 23.366 1.00 0.00C ATOM 527 OE1 GLN M 252 5.266 −13.790 23.431 1.00 0.00 O ATOM 528 NE2GLN M 252 5.051 −15.838 22.419 1.00 0.00 N ATOM 529 N ILE M 255 0.964−14.328 28.520 1.00 0.00 N ATOM 530 CA ILE M 255 −0.102 −14.190 27.5161.00 0.00 C ATOM 531 C ILE M 255 −0.955 −15.467 27.497 1.00 0.00 C ATOM532 O ILE M 255 −2.176 −15.390 27.471 1.00 0.00 O ATOM 533 CB ILE M 2550.417 −13.804 26.101 1.00 0.00 C ATOM 534 CG1 ILE M 255 1.209 −12.47626.083 1.00 0.00 C ATOM 535 CG2 ILE M 255 −0.717 −13.748 25.070 1.000.00 C ATOM 536 CD1 ILE M 255 0.452 −11.258 26.598 1.00 0.00 C ATOM 537N PHE M 256 −0.261 −16.672 27.484 1.00 0.00 N ATOM 538 CA PHE M 256−0.946 −17.970 27.541 1.00 0.00 C ATOM 539 C PHE M 256 −1.898 −18.03228.747 1.00 0.00 C ATOM 540 O PHE M 256 −3.034 −18.468 28.616 1.00 0.00O ATOM 541 CB PHE M 256 0.059 −19.141 27.510 1.00 0.00 C ATOM 542 CG PHEM 256 −0.534 −20.518 27.696 1.00 0.00 C ATOM 543 CD1 PHE M 256 −0.013−21.386 28.689 1.00 0.00 C ATOM 544 CD2 PHE M 256 −1.597 −20.985 26.8821.00 0.00 C ATOM 545 CE1 PHE M 256 −0.539 −22.680 28.863 1.00 0.00 CATOM 546 CE2 PHE M 256 −2.128 −22.276 27.065 1.00 0.00 C ATOM 547 CZ PHEM 256 −1.597 −23.125 28.052 1.00 0.00 C ATOM 548 N LEU M 259 −5.058−16.050 26.251 1.00 0.00 N ATOM 549 CA LEU M 259 −5.940 −16.735 27.3081.00 0.00 C ATOM 550 C LEU M 259 −6.805 −17.754 28.046 1.00 0.00 C ATOM551 O LEU M 259 −8.018 −17.761 27.887 1.00 0.00 O ATOM 552 CB LEU M 259−5.159 −17.348 26.128 1.00 0.00 C ATOM 553 CG LEU M 259 −6.050 −17.85624.974 1.00 0.00 C ATOM 554 CD1 LEU M 259 −5.327 −17.681 23.640 1.000.00 C ATOM 555 CD2 LEU M 259 −6.433 −19.328 25.144 1.00 0.00 C ATOM 556N ILE M 205 −1.811 −26.903 22.691 1.00 0.00 N ATOM 557 CA ILE M 205−0.778 −27.375 21.760 1.00 0.00 C ATOM 558 C ILE M 205 −0.407 −26.24220.791 1.00 0.00 C ATOM 559 O ILE M 205 0.770 −25.964 20.598 1.00 0.00 OATOM 560 CB ILE M 205 −1.070 −28.769 21.130 1.00 0.00 C ATOM 561 CG1 ILEM 205 0.183 −29.444 20.526 1.00 0.00 C ATOM 562 CG2 ILE M 205 −2.263−28.819 20.179 1.00 0.00 C ATOM 563 CD1 ILE M 205 0.576 −29.023 19.1151.00 0.00 C ATOM 564 N SER M 208 1.542 −23.361 22.633 1.00 0.00 N ATOM565 CA SER M 208 2.900 −23.765 22.998 1.00 0.00 C ATOM 566 C SER M 2083.883 −23.597 21.833 1.00 0.00 C ATOM 567 O SER M 208 5.032 −23.24722.054 1.00 0.00 O ATOM 568 CB SER M 208 2.985 −25.173 23.602 1.00 0.00C ATOM 569 OG SER M 208 2.785 −26.197 22.634 1.00 0.00 O

TABLE 6 ATOM 1 N ILE K 5 27.058 −0.783 12.427 1.00 0.00 N ATOM 2 CA ILEK 5 26.005 −1.691 12.91 1.00 0.00 C ATOM 3 C ILE K 5 24.924 −0.88113.636 1.00 0.00 C ATOM 4 O ILE K 5 23.769 −1.281 13.67 1.00 0.00 O ATOM5 CB ILE K 5 26.579 −2.844 13.786 1.00 0.00 C ATOM 6 CG1 ILE K 5 25.508−3.932 14.021 1.00 0.00 C ATOM 7 CG2 ILE K 5 27.182 −2.353 15.11 1.000.00 C ATOM 8 CD1 ILE K 5 26.069 −5.224 14.594 1.00 0.00 C ATOM 21 N ALAK 6 25.369 0.283 14.253 1.00 0.00 N ATOM 22 CA ALA K 6 24.511 1.12815.082 1.00 0.00 C ATOM 23 C ALA K 6 23.265 1.544 14.305 1.00 0.00 CATOM 24 O ALA K 6 22.147 1.344 14.761 1.00 0.00 O ATOM 25 CB ALA K 625.244 2.356 15.619 1.00 0.00 C ATOM 31 N ALA K 7 23.517 2.156 13.0811.00 0.00 N ATOM 32 CA ALA K 7 22.441 2.61 12.201 1.00 0.00 C ATOM 33 CALA K 7 21.495 1.458 11.876 1.00 0.00 C ATOM 34 O ALA K 7 20.285 1.61911.95 1.00 0.00 O ATOM 35 CB ALA K 7 22.963 3.241 10.913 1.00 0.00 CATOM 41 N GLY K 8 22.114 0.275 11.484 1.00 0.00 N ATOM 42 CA GLY K 821.387 −0.928 11.111 1.00 0.00 C ATOM 43 C GLY K 8 20.361 −1.344 12.151.00 0.00 C ATOM 44 O GLY K 8 19.223 −1.636 11.812 1.00 0.00 O ATOM 48 NALA K 9 20.834 −1.403 13.453 1.00 0.00 N ATOM 49 CA ALA K 9 19.997−1.824 14.574 1.00 0.00 C ATOM 50 C ALA K 9 18.758 −0.942 14.691 1.000.00 C ATOM 51 O ALA K 9 17.646 −1.449 14.766 1.00 0.00 O ATOM 52 CB ALAK 9 20.76 −1.855 15.898 1.00 0.00 C ATOM 58 N LEU K 10 18.999 0.42614.75 1.00 0.00 N ATOM 59 CA LEU K 10 17.924 1.389 15 1.00 0.00 C ATOM60 C LEU K 10 16.887 1.33 13.879 1.00 0.00 C ATOM 61 O LEU K 10 15.71.191 14.146 1.00 0.00 O ATOM 62 CB LEU K 10 18.423 2.836 15.198 1.000.00 C ATOM 63 CG LEU K 10 18.696 3.198 16.672 1.00 0.00 C ATOM 64 CD1LEU K 10 19.859 2.414 17.278 1.00 0.00 C ATOM 65 CD2 LEU K 10 18.9694.695 16.798 1.00 0.00 C ATOM 77 N ILE K 11 17.378 1.5 12.587 1.00 0.00N ATOM 78 CA ILE K 11 16.48 1.562 11.429 1.00 0.00 C ATOM 79 C ILE K 1115.7 0.252 11.263 1.00 0.00 C ATOM 80 O ILE K 11 14.534 0.274 10.8961.00 0.00 O ATOM 81 CB ILE K 11 17.176 2.041 10.122 1.00 0.00 C ATOM 82CG1 ILE K 11 16.131 2.575 9.12 1.00 0.00 C ATOM 83 CG2 ILE K 11 18.0550.966 9.473 1.00 0.00 C ATOM 84 CD1 ILE K 11 16.741 3.382 7.984 1.000.00 C ATOM 96 N GLY K 12 16.41 −0.914 11.531 1.00 0.00 N ATOM 97 CA GLYK 12 15.813 −2.237 11.499 1.00 0.00 C ATOM 98 C GLY K 12 14.611 −2.30312.416 1.00 0.00 C ATOM 99 O GLY K 12 13.536 −2.709 12 1.00 0.00 O ATOM103 N GLY K 13 14.846 −1.88 13.717 1.00 0.00 N ATOM 104 CA GLY K 1313.807 −1.823 14.732 1.00 0.00 C ATOM 105 C GLY K 13 12.578 −1.07214.253 1.00 0.00 C ATOM 106 O GLY K 13 11.46 −1.551 14.387 1.00 0.00 OATOM 110 N GLY K 14 12.838 0.172 23.697 1.00 0.00 N ATOM 111 CA GLY K 1411.798 1.03 13.153 1.00 0.00 C ATOM 112 C GLY K 14 10.931 0.316 12.1281.00 0.00 C ATOM 113 O GLY K 14 9.712 0.341 12.22 1.00 0.00 O ATOM 117 NLEU K 15 11.635 −0.303 11.102 1.00 0.00 N ATOM 118 CA LEU K 15 10.993−1.025 9.999 1.00 0.00 C ATOM 119 C LEU K 15 10.067 −2.105 10.557 1.000.00 C ATOM 120 O LEU K 15 8.915 −2.197 10.152 1.00 0.00 O ATOM 121 CBLEU K 15 12.035 −1.587 9.004 1.00 0.00 C ATOM 122 CG LEU K 15 11.445−2.194 7.711 1.00 0.00 C ATOM 123 CD1 LEU K 15 12.428 −2.021 6.554 1.000.00 C ATOM 124 CD2 LEU K 15 11.123 −3.683 7.861 1.00 0.00 C ATOM 136 NILE K 16 10.642 −2.954 11.496 1.00 0.00 N ATOM 137 CA ILE K 16 9.942−4.097 12.092 1.00 0.00 C ATOM 138 C ILE K 16 8.626 −3.603 12.7 1.000.00 C ATOM 139 O ILE K 16 7.571 −4.156 12.418 1.00 0.00 O ATOM 140 CBILE K 16 10.83 −4.875 13.109 1.00 0.00 C ATOM 141 CG1 ILE K 16 11.973−5.618 12.381 1.00 0.00 C ATOM 142 CG2 ILE K 16 10.018 −5.879 13.9351.00 0.00 C ATOM 143 CD1 ILE K 16 13.148 −5.927 13.297 1.00 0.00 C ATOM155 N MET K 17 8.739 −2.545 13.594 1.00 0.00 N ATOM 156 CA MET K 177.591 −2.019 14.334 1.00 0.00 C ATOM 157 C MET K 17 6.504 −1.535 13.3811.00 0.00 C ATOM 158 O MET K 17 5.348 −1.902 13.537 1.00 0.00 O ATOM 159CB MET K 17 7.962 −0.901 15.322 1.00 0.00 C ATOM 160 CG MET K 17 8.601−1.47 16.585 1.00 0.00 C ATOM 161 SD MET K 17 8.93 −0.146 17.788 1.000.00 S ATOM 162 CE MET K 17 10.614 0.288 17.282 1.00 0.00 C ATOM 172 NALA K 18 6.911 −0.636 12.403 1.00 0.00 N ATOM 173 CA ALA K 18 5.9640.011 11.493 1.00 0.00 C ATOM 174 C ALA K 18 5.188 −1.023 10.677 1.000.00 C ATOM 175 O ALA K 18 3.97 −0.95 10.578 1.00 0.00 O ATOM 176 CB ALAK 18 6.641 1.021 10.569 1.00 0.00 C ATOM 182 N GLY K 19 5.967 −1.99110.054 1.00 0.00 N ATOM 183 CA GLY K 19 5.408 −3.043 9.218 1.00 0.00 CATOM 184 C GLY K 19 4.394 −3.878 9.977 1.00 0.00 C ATOM 185 O GLY K 193.286 −4.103 9.508 1.00 0.00 O ATOM 189 N GLY K 20 4.848 −4.359 11.1971.00 0.00 N ATOM 190 CA GLY K 20 4.021 −5.15 12.09 1.00 0.00 C ATOM 191C GLY K 20 2.697 −4.472 12.392 1.00 0.00 C ATOM 192 O GLY K 20 1.647−5.091 12.298 1.00 0.00 O ATOM 196 N ALA K 21 2.806 −3.152 12.809 1.000.00 N ATOM 197 CA ALA K 21 1.667 −2.358 13.263 1.00 0.00 C ATOM 198 CALA K 21 0.567 −2.315 12.213 1.00 0.00 C ATOM 199 O ALA K 21 −0.577−2.642 12.5 1.00 0.00 O ATOM 200 CB ALA K 21 2.064 −0.934 13.646 1.000.00 C ATOM 206 N ILE K 22 0.955 −1.827 10.97 1.00 0.00 N ATOM 207 CAILE K 22 −0.025 −1.608 9.903 1.00 0.00 C ATOM 208 C ILE K 22 −0.652−2.932 9.466 1.00 0.00 C ATOM 209 O ILE K 22 −1.843 −2.981 9.19 1.000.00 O ATOM 210 CB ILE K 22 0.469 −0.726 8.719 1.00 0.00 C ATOM 211 CG1ILE K 22 1.644 −1.303 7.896 1.00 0.00 C ATOM 212 CG2 ILE K 22 0.837 0.679.233 1.00 0.00 C ATOM 213 CD1 ILE K 22 1.194 −2.103 6.683 1.00 0.00 CATOM 225 N GLY K 23 0.203 −4.026 9.4 1.00 0.00 N ATOM 226 CA GLY K 23−0.258 −5.356 9.039 1.00 0.00 C ATOM 227 C GLY K 23 −1.377 −5.813 9.9521.00 0.00 C ATOM 228 O GLY K 23 −2.452 −6.173 9.493 1.00 0.00 O ATOM 232N ALA K 24 −1.053 −5.787 11.302 1.00 0.00 N ATOM 233 CA ALA K 24 −1.98−6.184 12.36 1.00 0.00 C ATOM 234 C ALA K 24 −3.307 −5.44 12.237 1.000.00 C ATOM 235 O ALA K 24 −4.364 −6.054 12.279 1.00 0.00 O ATOM 236 CBALA K 24 −1.384 −5.973 13.75 1.00 0.00 C ATOM 242 N GLY K 25 −3.208−4.059 12.109 1.00 0.00 N ATOM 243 CA GLY K 25 −4.364 −3.177 12.068 1.000.00 C ATOM 244 C GLY K 25 −5.351 −3.56 10.98 1.00 0.00 C ATOM 245 O GLYK 25 −6.536 −3.73 11.236 1.00 0.00 O ATOM 249 N ILE K 26 −4.796 −3.6579.709 1.00 0.00 N ATOM 250 CA ILE K 26 −5.591 −4.032 8.536 1.00 0.00 CATOM 251 C ILE K 26 −6.235 −5.396 8.795 1.00 0.00 C ATOM 252 O ILE K 26−7.416 −5.566 8.528 1.00 0.00 O ATOM 253 CB ILE K 26 −4.783 −4 7.2061.00 0.00 C ATOM 254 CG1 ILE K 26 −4.292 −2.579 6.838 1.00 0.00 C ATOM255 CG2 ILE K 26 −5.561 −4.608 6.032 1.00 0.00 C ATOM 256 CD1 ILE K 26−5.385 −1.554 6.559 1.00 0.00 C ATOM 268 N GLY K 27 −5.397 −6.38 9.3071.00 0.00 N ATOM 269 CA GLY K 27 −5.83 −7.74 9.594 1.00 0.00 C ATOM 270C GLY K 27 −7.112 −7.787 10.405 1.00 0.00 C ATOM 271 O GLY K 27 −8.07−8.439 10.013 1.00 0.00 O ATOM 275 N ASP K 28 −7.077 −7.058 11.591 1.000.00 N ATOM 276 CA ASP K 28 −8.223 −6.975 12.505 1.00 0.00 C ATOM 277 CASP K 28 −9.482 −6.599 11.738 1.00 0.00 C ATOM 278 O ASP K 28 −10.514−7.236 11.903 1.00 0.00 O ATOM 279 CB ASP K 28 −8.039 −5.969 13.656 1.000.00 C ATOM 280 CG ASP K 28 −7.187 −6.544 14.754 1.00 0.00 C ATOM 281OD1 ASP K 28 −5.972 −6.441 14.829 1.00 0.00 O ATOM 282 OD2 ASP K 28−7.946 −7.253 15.625 1.00 0.00 O ATOM 288 N GLY K 29 −9.359 −5.49210.907 1.00 0.00 N ATOM 289 CA GLY K 29 −10.461 −4.983 10.114 1.00 0.00C ATOM 290 C GLY K 29 −11.002 −6.071 9.208 1.00 0.00 C ATOM 291 O GLY K29 −12.083 −6.597 9.429 1.00 0.00 O ATOM 295 N VAL K 30 −10.178 −6.3998.143 1.00 0.00 N ATOM 296 CA VAL K 30 −10.67 −7.186 7.009 1.00 0.00 CATOM 297 C VAL K 30 −11.213 −8.543 7.465 1.00 0.00 C ATOM 298 O VAL K 30−12.315 −8.919 7.092 1.00 0.00 O ATOM 299 CB VAL K 30 −9.698 −7.303 5.81.00 0.00 C ATOM 300 CG1 VAL K 30 −9.406 −5.926 5.198 1.00 0.00 C ATOM301 CG2 VAL K 30 −8.382 −8.03 6.091 1.00 0.00 C ATOM 311 N ALA K 31−10.37 −9.299 8.271 1.00 0.00 N ATOM 312 CA ALA K 31 −10.706 −10.6678.665 1.00 0.00 C ATOM 313 C ALA K 31 −11.898 −10.686 9.618 1.00 0.00 CATOM 314 O ALA K 31 −12.803 −11.495 9.46 1.00 0.00 O ATOM 315 CB ALA K31 −9.525 −11.407 9.286 1.00 0.00 C ATOM 321 N GLY K 32 −11.834 −9.77910.669 1.00 0.00 N ATOM 322 CA GLY K 32 −12.843 −9.719 11.713 1.00 0.00C ATOM 323 C GLY K 32 −14.212 −9.398 11.15 1.00 0.00 C ATOM 324 O GLY K32 −15.182 −10.089 11.427 1.00 0.00 O ATOM 328 N ASN K 33 −14.267 −8.25710.363 1.00 0.00 N ATOM 329 CA ASN K 33 −15.523 −7.785 9.783 1.00 0.00 CATOM 330 C ASN K 33 −16.1 −8.775 8.775 1.00 0.00 C ATOM 331 O ASN K 33−17.312 −8.902 8.669 1.00 0.00 O ATOM 332 CB ASN K 33 −15.438 −6.399.141 1.00 0.00 C ATOM 333 CG ASN K 33 −15.197 −5.297 10.168 1.00 0.00 CATOM 334 OD1 ASN K 33 −14.133 −4.701 10.251 1.00 0.00 O ATOM 335 ND2 ASNK 33 −16.269 −5.042 10.995 1.00 0.00 N ATOM 342 N ALA K 34 −15.199−9.465 7.974 1.00 0.00 N ATOM 343 CA ALA K 34 −15.658 −10.508 7.052 1.000.00 C ATOM 344 C ALA K 34 −16.41 −11.608 7.806 1.00 0.00 C ATOM 345 OALA K 34 −17.483 −12.02 7.386 1.00 0.00 O ATOM 346 CB ALA K 34 −14.527−11.101 6.219 1.00 0.00 C ATOM 352 N LEU K 35 −15.783 −12.094 8.95 1.000.00 N ATOM 353 CA LEU K 35 −16.377 −13.139 9.789 1.00 0.00 C ATOM 354 CLEU K 35 −17.768 −12.695 10.244 1.00 0.00 C ATOM 355 O LEU K 35 −18.742−13.411 10.043 1.00 0.00 O ATOM 356 CB LEU K 35 −15.479 −13.513 10.991.00 0.00 C ATOM 357 CG LEU K 35 −16.052 −14.618 11.902 1.00 0.00 C ATOM358 CD1 LEU K 35 −16.009 −15.99 11.23 1.00 0.00 C ATOM 359 CD2 LEU K 35−15.276 −14.658 13.216 1.00 0.00 C ATOM 371 N ILE K 36 −17.815 −11.47810.924 1.00 0.00 N ATOM 372 CA ILE K 36 −19.036 −11.013 11.585 1.00 0.00C ATOM 373 C ILE K 36 −20.189 −10.855 10.589 1.00 0.00 C ATOM 374 O ILEK 36 −21.332 −11.098 10.941 1.00 0.00 O ATOM 375 CB ILE K 36 −18.824−9.757 12.487 1.00 0.00 C ATOM 376 CG1 ILE K 36 −19.806 −9.719 13.6761.00 0.00 C ATOM 377 CG2 ILE K 36 −18.929 −8.435 11.725 1.00 0.00 C ATOM378 CD1 ILE K 36 −19.42 −10.675 14.794 1.00 0.00 C ATOM 390 N SER K 37−19.865 −10.405 9.312 1.00 0.00 N ATOM 391 CA SER K 37 −20.884 −10.1868.284 1.00 0.00 C ATOM 392 C SER K 37 −21.815 −11.397 8.16 1.00 0.00 CATOM 393 O SER K 37 −23.023 −11.239 8.041 1.00 0.00 O ATOM 394 CB SER K37 −20.287 −9.841 6.914 1.00 0.00 C ATOM 395 OG SER K 37 −19.614 −8.5846.969 1.00 0.00 O ATOM 401 N GLY K 38 −21.186 −12.637 8.153 1.00 0.00 NATOM 402 CA GLY K 38 −21.939 −13.876 8.213 1.00 0.00 C ATOM 403 C GLY K38 −22.605 −14.037 9.569 1.00 0.00 C ATOM 404 O GLY K 38 −23.824 −14.0179.682 1.00 0.00 O ATOM 408 N VAL K 39 −21.718 −14.263 10.616 1.00 0.00 NATOM 409 CA VAL K 39 −22.168 −14.679 11.946 1.00 0.00 C ATOM 410 C VAL K39 −22.563 −13.39 12.682 1.00 0.00 C ATOM 411 O VAL K 39 −21.756 −12.74813.341 1.00 0.00 O ATOM 412 CB VAL K 39 −21.084 −15.481 12.719 1.00 0.00C ATOM 413 CG1 VAL K 39 −21.656 −16.043 14.02 1.00 0.00 C ATOM 414 CG2VAL K 39 −20.526 −16.646 11.894 1.00 0.00 C ATOM 424 N ALA K 40 −23.894−13.035 12.506 1.00 0.00 N ATOM 425 CA ALA K 40 −24.463 −11.774 13.0061.00 0.00 C ATOM 426 C ALA K 40 −25.936 −11.94 13.362 1.00 0.00 C ATOM427 O ALA K 40 −26.358 −11.554 14.443 1.00 0.00 O ATOM 428 CB ALA K 40−24.298 −10.61 12.033 1.00 0.00 C ATOM 434 N ARG K 41 −26.737 −12.49612.37 1.00 0.00 N ATOM 435 CA ARG K 41 −28.114 −12.909 12.642 1.00 0.00C ATOM 436 C ARG K 41 −28.115 −14.033 13.684 1.00 0.00 C ATOM 437 O ARGK 41 −28.983 −14.075 14.545 1.00 0.00 O ATOM 438 CB ARG K 41 −28.899−13.343 11.39 1.00 0.00 C ATOM 439 CG ARG K 41 −29.26 −12.176 10.4581.00 0.00 C ATOM 440 CD ARG K 41 −28.242 −11.958 9.338 1.00 0.00 C ATOM441 NE ARG K 41 −28.568 −10.728 8.596 1.00 0.00 N ATOM 442 CZ ARG K 41−28.108 −9.468 8.913 1.00 0.00 C ATOM 443 NH1 ARG K 41 −27.365 −9.17910.037 1.00 0.00 N ATOM 444 NH2 ARG K 41 −28.387 −8.41 8.087 1.00 0.00 NATOM 457 N GLN K 42 −27.106 −14.986 13.554 1.00 0.00 N ATOM 458 CA GLN K42 −26.838 −15.971 14.603 1.00 0.00 C ATOM 459 C GLN K 42 −26.427−15.168 15.845 1.00 0.00 C ATOM 460 O GLN K 42 −25.66 −14.219 15.7361.00 0.00 O ATOM 461 CB GLN K 42 −25.692 −16.926 14.241 1.00 0.00 C ATOM462 CG GLN K 42 −26.038 −17.841 13.067 1.00 0.00 C ATOM 463 CD GLN K 42−24.858 −18.734 12.753 1.00 0.00 C ATOM 464 OE1 GLN K 42 −23.974 −18.39411.98 1.00 0.00 O ATOM 465 NE2 GLN K 42 −24.852 −19.924 13.446 1.00 0.00N ATOM 474 N PRO K 43 −26.929 −15.616 17.076 1.00 0.00 N ATOM 475 CA PROK 43 −26.718 −14.888 18.317 1.00 0.00 C ATOM 476 C PRO K 43 −25.257−14.537 18.565 1.00 0.00 C ATOM 477 O PRO K 43 −24.341 −15.313 18.3041.00 0.00 O ATOM 478 CB PRO K 43 −27.219 −15.818 19.412 1.00 0.00 C ATOM479 CG PRO K 43 −28.251 −16.685 18.727 1.00 0.00 C ATOM 480 CD PRO K 43−27.812 −16.751 17.277 1.00 0.00 C ATOM 488 N GLU K 44 −25.104 −13.30419.191 1.00 0.00 N ATOM 489 CA GLU K 44 −23.821 −12.843 19.719 1.00 0.00C ATOM 490 C GLU K 44 −23.618 −13.555 21.061 1.00 0.00 C ATOM 491 O GLUK 44 −23.904 −13.05 22.137 1.00 0.00 O ATOM 492 CB GLU K 44 −23.689−11.309 19.801 1.00 0.00 C ATOM 493 CG GLU K 44 −24.829 −10.561 20.5011.00 0.00 C ATOM 494 CD GLU K 44 −24.464 −9.106 20.633 1.00 0.00 C ATOM495 OE1 GLU K 44 −24.639 −8.26 19.768 1.00 0.00 O ATOM 496 OE2 GLU K 44−23.844 −8.861 21.816 1.00 0.00 O ATOM 504 N ALA K 45 −23.108 −14.83220.905 1.00 0.00 N ATOM 505 CA ALA K 45 −22.829 −15.746 22.006 1.00 0.00C ATOM 506 C ALA K 45 −21.818 −16.757 21.467 1.00 0.00 C ATOM 507 O ALAK 45 −20.672 −16.776 21.891 1.00 0.00 O ATOM 508 CB ALA K 45 −24.083−16.4 22.583 1.00 0.00 C ATOM 514 N GLN K 46 −22.284 −17.575 20.441 1.000.00 N ATOM 515 CA GLN K 46 −21.387 −18.407 19.636 1.00 0.00 C ATOM 516C GLN K 46 −20.471 −17.482 18.834 1.00 0.00 C ATOM 517 O GLN K 46−19.257 −17.639 18.851 1.00 0.00 O ATOM 518 CB GLN K 46 −22.133 −19.37318.697 1.00 0.00 C ATOM 519 CG GLN K 46 −22.759 −20.568 19.422 1.00 0.00C ATOM 520 CD GLN K 46 −23.88 −20.164 20.364 1.00 0.00 C ATOM 521 OE1GLN K 46 −24.797 −19.434 20.015 1.00 0.00 O ATOM 522 NE2 GLN K 46−23.776 −20.701 21.628 1.00 0.00 N ATOM 531 N GLY K 47 −21.113 −16.48118.113 1.00 0.00 N ATOM 532 CA GLY K 47 −20.379 −15.473 17.363 1.00 0.00C ATOM 533 C GLY K 47 −19.364 −14.732 18.212 1.00 0.00 C ATOM 534 O GLYK 47 −18.227 −14.543 17.801 1.00 0.00 O ATOM 538 N ARG K 48 −19.851−14.254 19.419 1.00 0.00 N ATOM 539 CA ARG K 48 −19.045 −13.46 20.3421.00 0.00 C ATOM 540 C ARG K 48 −17.993 −14.261 21.128 1.00 0.00 C ATOM541 O ARG K 48 −17.214 −13.663 21.854 1.00 0.00 O ATOM 542 CB ARG K 48−19.954 −12.677 21.313 1.00 0.00 C ATOM 543 CG ARG K 48 −19.359 −11.32421.726 1.00 0.00 C ATOM 544 CD ARG K 48 −20.308 −10.519 22.607 1.00 0.00C ATOM 545 NE ARG K 48 −20.356 −11.117 23.953 1.00 0.00 N ATOM 546 CZARG K 48 −21.46 −11.2 24.769 1.00 0.00 C ATOM 547 NH1 ARG K 48 −22.727−10.788 24.417 1.00 0.00 N ATOM 548 NH2 ARG K 48 −21.325 −11.724 26.0321.00 0.00 N ATOM 561 N LEU K 49 −17.971 −15.646 20.987 1.00 0.00 N ATOM562 CA LEU K 49 −16.83 −16.458 21.424 1.00 0.00 C ATOM 563 C LEU K 49−15.744 −16.45 20.342 1.00 0.00 C ATOM 564 O LEU K 49 −14.582 −16.19220.63 1.00 0.00 O ATOM 565 CB LEU K 49 −17.252 −17.894 21.798 1.00 0.00C ATOM 566 CG LEU K 49 −16.109 −18.79 22.321 1.00 0.00 C ATOM 567 CD1LEU K 49 −15.498 −18.26 23.619 1.00 0.00 C ATOM 568 CD2 LEU K 49 −16.627−20.209 22.542 1.00 0.00 C ATOM 580 N PHE K 50 −16.16 −16.818 19.0641.00 0.00 N ATOM 581 CA PHE K 50 −15.203 −17.015 17.967 1.00 0.00 C ATOM582 C PHE K 50 −14.483 −15.701 17.636 1.00 0.00 C ATOM 583 O PHE K 50−13.28 −15.693 17.411 1.00 0.00 O ATOM 584 CB PHE K 50 −15.847 −17.6216.692 1.00 0.00 C ATOM 585 CG PHE K 50 −15.074 −18.773 16.077 1.00 0.00C ATOM 586 CD1 PHE K 50 −13.675 −18.707 15.835 1.00 0.00 C ATOM 587 CE1PHE K 50 −12.985 −19.792 15.262 1.00 0.00 C ATOM 588 CZ PHE K 50 −13.679−20.958 14.898 1.00 0.00 C ATOM 589 CE2 PHE K 50 −15.066 −21.038 15.1111.00 0.00 C ATOM 590 CD2 PHE K 50 −15.757 −19.958 15.696 1.00 0.00 CATOM 600 N THR K 51 −15.291 −14.571 17.559 1.00 0.00 N ATOM 601 CA THR K51 −14.79 −13.258 17.147 1.00 0.00 C ATOM 602 C THR K 51 −13.543 −12.86717.958 1.00 0.00 C ATOM 603 O THR K 51 −12.534 −12.554 17.343 1.00 0.00O ATOM 604 CB THR K 51 −15.891 −12.173 17.107 1.00 0.00 C ATOM 605 OG1THR K 51 −16.873 −12.559 16.143 1.00 0.00 O ATOM 606 CG2 THR K 51−15.364 −10.808 16.678 1.00 0.00 C ATOM 614 N PRO K 52 −13.59 −12.89719.362 1.00 0.00 N ATOM 615 CA PRO K 52 −12.407 −12.708 20.183 1.00 0.00C ATOM 616 C PRO K 52 −11.143 −13.421 19.738 1.00 0.00 C ATOM 617 O PROK 52 −10.081 −12.818 19.762 1.00 0.00 O ATOM 618 CB PRO K 52 −12.818−13.12 21.581 1.00 0.00 C ATOM 619 CG PRO K 52 −14.286 −12.768 21.631.00 0.00 C ATOM 620 CD PRO K 52 −14.776 −12.857 20.191 1.00 0.00 C ATOM628 N PHE K 53 −11.273 −14.753 19.362 1.00 0.00 N ATOM 629 CA PHE K 53−10.108 −15.537 18.945 1.00 0.00 C ATOM 630 C PHE K 53 −9.437 −14.8517.749 1.00 0.00 C ATOM 631 O PHE K 53 −8.235 −14.619 17.761 1.00 0.00 OATOM 632 CB PHE K 53 −10.436 −17.016 18.655 1.00 0.00 C ATOM 633 CG PHEK 53 −9.193 −17.873 18.699 1.00 0.00 C ATOM 634 CD1 PHE K 53 −8.387−18.048 17.547 1.00 0.00 C ATOM 635 CD2 PHE K 53 −8.795 −18.497 19.911.00 0.00 C ATOM 636 CE1 PHE K 53 −7.202 −18.805 17.612 1.00 0.00 C ATOM637 CE2 PHE K 53 −7.613 19.261 19.968 1.00 0.00 C ATOM 638 CZ PHE K 53−6.813 −19.409 18.822 1.00 0.00 C ATOM 648 N PHE K 54 −10.273 −14.53516.683 1.00 0.00 N ATOM 649 CA PHE K 54 −9.772 −13.883 15.468 1.00 0.00C ATOM 650 C PHE K 54 −9.045 −12.59 15.844 1.00 0.00 C ATOM 651 O PHE K54 −7.885 −12.404 15.497 1.00 0.00 O ATOM 652 CB PHE K 54 −10.875−13.584 14.425 1.00 0.00 C ATOM 653 CG PHE K 54 −11.049 −14.675 13.3951.00 0.00 C ATOM 654 CD1 PHE K 54 −10.674 −14.445 12.046 1.00 0.00 CATOM 655 CD2 PHE K 54 −11.619 −15.927 13.735 1.00 0.00 C ATOM 656 CE1PHE K 54 −10.872 −15.433 11.064 1.00 0.00 C ATOM 657 CE2 PHE K 54−11.815 −16.915 12.749 1.00 0.00 C ATOM 658 CZ PHE K 54 −11.446 −16.66811.415 1.00 0.00 C ATOM 668 N ILE K 55 −9.806 −11.654 16.535 1.00 0.00 NATOM 669 CA ILE K 55 −9.312 −10.293 16.755 1.00 0.00 C ATOM 670 C ILE K55 −8.091 −10.238 17.676 1.00 0.00 C ATOM 671 O ILE K 55 −7.254 −9.36517.494 1.00 0.00 O ATOM 672 CB ILE K 55 −10.389 −9.246 17.158 1.00 0.00C ATOM 673 CG1 ILE K 55 −11.082 −9.542 18.501 1.00 0.00 C ATOM 674 CG2ILE K 55 −11.412 −9.083 16.026 1.00 0.00 C ATOM 675 CD1 ILE K 55 −11.891−8.371 19.037 1.00 0.00 C ATOM 687 N THR K 56 −8.023 −11.158 18.719 1.000.00 N ATOM 688 CA THR K 56 −6.895 −11.169 19.652 1.00 0.00 C ATOM 689 CTHR K 56 −5.609 −11.585 18.936 1.00 0.00 C ATOM 690 O THR K 56 −4.563−11.008 19.195 1.00 0.00 O ATOM 691 CB THR K 56 −7.163 −11.948 20.9671.00 0.00 C ATOM 692 OG1 THR K 56 −6.253 −11.504 21.975 1.00 0.00 O ATOM693 CG2 THR K 56 −7.019 −13.463 20.88 1.00 0.00 C ATOM 701 N VAL K 57−5.703 −12.634 18.023 1.00 0.00 N ATOM 702 CA VAL K 57 −4.544 −13.06517.229 1.00 0.00 C ATOM 703 C VAL K 57 −4.032 −11.845 16.459 1.00 0.00 CATOM 704 O VAL K 57 −2.852 −11.526 16.523 1.00 0.00 O ATOM 705 CB VAL K57 −4.84 −14.286 16.314 1.00 0.00 C ATOM 706 CG1 VAL K 57 −3.727 −14.53815.293 1.00 0.00 C ATOM 707 CG2 VAL K 57 −5.023 −15.555 17.15 1.00 0.00C ATOM 717 N GLY K 58 −4.99 −11.166 15.714 1.00 0.00 N ATOM 718 CA GLY K58 −4.679 −9.985 14.925 1.00 0.00 C ATOM 719 C GLY K 58 −3.929 −8.94215.735 1.00 0.00 C ATOM 720 O GLY K 58 −2.85 −8.511 15.357 1.00 0.00 OATOM 724 N LEU K 59 −4.583 −8.526 16.885 1.00 0.00 N ATOM 725 CA LEU K59 −4.116 −7.424 17.724 1.00 0.00 C ATOM 726 C LEU K 59 −2.71 −7.72118.236 1.00 0.00 C ATOM 727 O LEU K 59 −1.8 −6.932 18.027 1.00 0.00 OATOM 728 CB LEU K 59 −5.098 −7.132 18.879 1.00 0.00 C ATOM 729 CG LEU K59 −4.681 −5.985 19.821 1.00 0.00 C ATOM 730 CD1 LEU K 59 −4.63 −4.63719.101 1.00 0.00 C ATOM 731 CD2 LEU K 59 −5.655 −5.908 20.995 1.00 0.00C ATOM 743 N VAL K 60 −2.591 −8.892 18.977 1.00 0.00 N ATOM 744 CA VAL K60 −1.393 −9.246 19.745 1.00 0.00 C ATOM 745 C VAL K 60 −0.188 −9.55818.832 1.00 0.00 C ATOM 746 O VAL K 60 0.948 −9.523 19.287 1.00 0.00 OATOM 747 CB VAL K 60 −1.685 −10.355 20.8 1.00 0.00 C ATOM 748 CG1 VAL K60 −0.456 −10.725 21.631 1.00 0.00 C ATOM 749 CG2 VAL K 60 −2.775 −9.90521.784 1.00 0.00 C ATOM 759 N GLU K 61 −0.455 −9.815 17.489 1.00 0.00 NATOM 760 CA GLU K 61 0.601 −9.873 16.474 1.00 0.00 C ATOM 761 C GLU K 611.585 −8.71 16.652 1.00 0.00 C ATOM 762 O GLU K 61 2.791 −8.922 16.6681.00 0.00 O ATOM 763 CB GLU K 61 0.034 −9.906 15.044 1.00 0.00 C ATOM764 CG GLU K 61 1.102 −10.157 13.982 1.00 0.00 C ATOM 765 CD GLU K 610.467 −10.196 12.615 1.00 0.00 C ATOM 766 OE1 GLU K 61 0.258 −9.21611.914 1.00 0.00 O ATOM 767 OE2 GLU K 61 0.092 −11.457 12.285 1.00 0.00O ATOM 775 N ALA K 62 1.013 −7.443 16.754 1.00 0.00 N ATOM 776 CA ALA K62 1.826 −6.232 16.847 1.00 0.00 C ATOM 777 C ALA K 62 2.804 −6.32418.027 1.00 0.00 C ATOM 778 O ALA K 62 4.001 −6.269 17.784 1.00 0.00 OATOM 779 CB ALA K 62 1.015 −4.938 16.813 1.00 0.00 C ATOM 785 N TYR K 644.126 −8.886 19.558 1.00 0.00 N ATOM 786 CA TYR K 64 5.22 −9.841 19.3281.00 0.00 C ATOM 787 C TYR K 64 6.395 −9.131 18.644 1.00 0.00 C ATOM 788O TYR K 64 7.533 −9.237 19.085 1.00 0.00 O ATOM 789 CB TYR K 64 4.841−11.101 18.517 1.00 0.00 C ATOM 790 CG TYR K 64 3.724 −11.949 19.0791.00 0.00 C ATOM 791 CD1 TYR K 64 3.57 −12.184 20.471 1.00 0.00 C ATOM792 CD2 TYR K 64 2.807 −12.559 18.186 1.00 0.00 C ATOM 793 CE1 TYR K 642.502 −12.959 20.955 1.00 0.00 C ATOM 794 CE2 TYR K 64 1.734 −13.33318.662 1.00 0.00 C ATOM 795 CZ TYR K 64 1.582 −13.517 20.051 1.00 0.00 CATOM 796 OH TYR K 64 0.51 −14.228 20.567 1.00 0.00 O ATOM 806 N PHE K 656.078 −8.42 17.493 1.00 0.00 N ATOM 807 CA PHE K 65 7.098 −7.715 16.7111.00 0.00 C ATOM 808 C PHE K 65 7.688 −6.509 17.443 1.00 0.00 C ATOM 809O PHE K 65 8.857 −6.2 17.252 1.00 0.00 O ATOM 810 CB PHE K 65 6.592−7.299 15.317 1.00 0.00 C ATOM 811 CG PHE K 65 6.386 −8.506 14.431 1.000.00 C ATOM 812 CD1 PHE K 65 7.499 −9.252 13.959 1.00 0.00 C ATOM 813CE1 PHE K 65 7.307 −10.424 13.206 1.00 0.00 C ATOM 814 CZ PHE K 65 6.007−10.858 12.9 1.00 0.00 C ATOM 815 CE2 PHE K 65 4.898 −10.111 13.33 1.000.00 C ATOM 816 CD2 PHE K 65 5.083 −8.939 14.087 1.00 0.00 C ATOM 826 NILE K 66 6.836 −5.797 18.28 1.00 0.00 N ATOM 827 CA ILE K 66 7.311 −4.6819.108 1.00 0.00 C ATOM 828 C ILE K 66 8.423 −5.216 20.012 1.00 0.00 CATOM 829 O ILE K 66 9.497 −4.635 20.061 1.00 0.00 O ATOM 830 CB ILE K 666.193 −3.949 19.908 1.00 0.00 C ATOM 831 CG1 ILE K 66 5.183 −3.27218.953 1.00 0.00 C ATOM 832 CG2 ILE K 66 6.784 −2.897 20.856 1.00 0.00 CATOM 833 CD1 ILE K 66 3.904 −2.827 19.648 1.00 0.00 C ATOM 845 N ASN K67 8.12 −6.351 20.758 1.00 0.00 N ATOM 846 CA ASN K 67 9.084 −6.9821.666 1.00 0.00 C ATOM 847 C ASN K 67 10.38 −7.338 20.946 1.00 0.00 CATOM 848 O ASN K 67 11.454 −7.126 21.491 1.00 0.00 O ATOM 849 CB ASN K67 8.543 −8.23 22.385 1.00 0.00 C ATOM 850 CG ASN K 67 7.77 −7.84323.631 1.00 0.00 C ATOM 851 OD1 ASN K 67 6.567 −7.632 23.619 1.00 0.00 OATOM 852 ND2 ASN K 67 8.555 −7.711 24.756 1.00 0.00 N ATOM 859 N LEU K68 10.249 −7.945 19.702 1.00 0.00 N ATOM 860 CA LEU K 68 11.409 −8.3618.903 1.00 0.00 C ATOM 861 C LEU K 68 12.342 −7.161 18.698 1.00 0.00 CATOM 862 O LEU K 68 13.529 −7.233 18.988 1.00 0.00 O ATOM 863 CB LEU K68 10.985 −9.036 17.579 1.00 0.00 C ATOM 864 CG LEU K 68 12.09 −9.87816.906 1.00 0.00 C ATOM 865 CD1 LEU K 68 11.462 −10.985 16.058 1.00 0.00C ATOM 866 CD2 LEU K 68 13.006 −9.04 16.015 1.00 0.00 C ATOM 878 N ALA K69 11.744 −6.024 18.167 1.00 0.00 N ATOM 879 CA ALA K 69 12.484 −4.78117.934 1.00 0.00 C ATOM 880 C ALA K 69 13.125 −4.241 19.216 1.00 0.00 CATOM 881 O ALA K 69 14.252 −3.764 19.191 1.00 0.00 O ATOM 882 CB ALA K69 11.606 −3.701 17.312 1.00 0.00 C ATOM 888 N PHE K 70 12.328 −4.320.354 1.00 0.00 N ATOM 889 CA PHE K 70 12.764 −3.853 21.679 1.00 0.00 CATOM 890 C PHE K 70 14.099 −4.515 22.02 1.00 0.00 C ATOM 891 O PHE K 7015.029 −3.848 22.445 1.00 0.00 O ATOM 892 CB PHE K 70 11.724 −4.15322.791 1.00 0.00 C ATOM 893 CG PHE K 70 11.511 −3.023 23.769 1.00 0.00 CATOM 894 CD1 PHE K 70 10.227 −2.434 23.901 1.00 0.00 C ATOM 895 CE1 PHEK 70 10.001 −1.403 24.831 1.00 0.00 C ATOM 896 CZ PHE K 70 11.054 −0.93625.635 1.00 0.00 C ATOM 897 CE2 PHE K 70 12.332 −1.512 25.521 1.00 0.00C ATOM 898 CD2 PHE K 70 12.559 −2.555 24.602 1.00 0.00 C ATOM 908 N METK 71 14.144 −5.895 21.855 1.00 0.00 N ATOM 909 CA MET K 71 15.311 −6.70222.213 1.00 0.00 C ATOM 910 C MET K 71 16.54 −6.268 21.42 1.00 0.00 CATOM 911 O MET K 71 17.617 −6.161 21.989 1.00 0.00 O ATOM 912 CB MET K71 15.074 −8.211 22.043 1.00 0.00 C ATOM 913 CG MET K 71 14.1 −8.74423.094 1.00 0.00 C ATOM 914 SD MET K 71 13.617 −10.446 22.689 1.00 0.00S ATOM 915 CE MET K 71 12.287 −10.632 23.901 1.00 0.00 C ATOM 925 N ALAK 72 16.354 −6.05 20.057 1.00 0.00 N ATOM 926 CA ALA K 72 17.447 −5.60519.185 1.00 0.00 C ATOM 927 C ALA K 72 18.091 −4.323 19.72 1.00 0.00 CATOM 928 O ALA K 72 19.307 −4.229 19.831 1.00 0.00 O ATOM 929 CB ALA K72 17.003 −5.411 17.736 1.00 0.00 C ATOM 935 N LEU K 73 17.199 −3.30420.035 1.00 0.00 N ATOM 936 CA LEU K 73 17.624 −2.018 20.597 1.00 0.00 CATOM 937 C LEU K 73 18.403 −2.272 21.888 1.00 0.00 C ATOM 938 O LEU K 7319.485 −1.735 22.075 1.00 0.00 O ATOM 939 CB LEU K 73 16.417 −1.069 20.81.00 0.00 C ATOM 940 CG LEU K 73 16.695 0.393 21.215 1.00 0.00 C ATOM941 CD1 LEU K 73 17.026 0.557 22.699 1.00 0.00 C ATOM 942 CD2 LEU K 7317.744 1.075 20.34 1.00 0.00 C ATOM 954 N PHE K 74 17.774 −3.097 22.811.00 0.00 N ATOM 955 CA PHE K 74 18.26 −3.297 24.171 1.00 0.00 C ATOM956 C PHE K 74 19.694 −3.832 24.176 1.00 0.00 C ATOM 957 O PHE K 7420.534 −3.302 24.891 1.00 0.00 O ATOM 958 CB PHE K 74 17.307 −4.19424.987 1.00 0.00 C ATOM 959 CG PHE K 74 17.521 −4.114 26.478 1.00 0.00 CATOM 960 CD1 PHE K 74 17.967 −5.242 27.209 1.00 0.00 C ATOM 961 CE1 PHEK 74 18.105 −5.172 28.609 1.00 0.00 C ATOM 962 CZ PHE K 74 17.815 −3.97929.293 1.00 0.00 C ATOM 963 CE2 PHE K 74 17.377 −2.851 28.579 1.00 0.00C ATOM 964 CD2 PHE K 74 17.224 −2.918 27.182 1.00 0.00 C ATOM 974 N VALK 75 19.946 −4.946 23.371 1.00 0.00 N ATOM 975 CA VAL K 75 21.272 −5.58523.333 1.00 0.00 C ATOM 976 C VAL K 75 22.348 −4.601 22.861 1.00 0.00 CATOM 977 O VAL K 75 23.447 −4.59 23.401 1.00 0.00 O ATOM 978 CB VAL K 7521.372 −6.94 22.573 1.00 0.00 C ATOM 979 CG1 VAL K 75 20.544 −8.02423.262 1.00 0.00 C ATOM 980 CG2 VAL K 75 21.017 −6.882 21.086 1.00 0.00C ATOM 990 N PHE K 76 21.997 −3.787 21.789 1.00 0.00 N ATOM 991 CA PHE K76 22.881 −2.742 21.272 1.00 0.00 C ATOM 992 C PHE K 76 23.25 −1.78922.416 1.00 0.00 C ATOM 993 O PHE K 76 24.423 −1.544 22.664 1.00 0.00 OATOM 994 CB PHE K 76 22.268 −2.031 20.042 1.00 0.00 C ATOM 995 CG PHE K76 22.877 −0.685 19.729 1.00 0.00 C ATOM 996 CD1 PHE K 76 22.154 0.50120.013 1.00 0.00 C ATOM 997 CD2 PHE K 76 24.174 −0.578 19.171 1.00 0.00C ATOM 998 CE1 PHE K 76 22.718 1.764 19.756 1.00 0.00 C ATOM 999 CE2 PHEK 76 24.736 0.689 18.92 1.00 0.00 C ATOM 1000 CZ PHE K 76 24.01 1.85819.211 1.00 0.00 C ATOM 1010 N ALA K 77 22.172 −1.217 23.081 1.00 0.00 NATOM 1011 CA ALA K 77 22.328 −0.136 24.048 1.00 0.00 C ATOM 1012 C ALA K77 23.234 −0.547 25.206 1.00 0.00 C ATOM 1013 O ALA K 77 24.165 0.17125.545 1.00 0.00 O ATOM 1014 CB ALA K 77 20.987 0.377 24.569 1.00 0.00 CATOM 1020 N THR K 78 22.88 −1.727 25.855 1.00 0.00 N ATOM 1021 CA THR K78 23.625 −2.223 27.009 1.00 0.00 C ATOM 1022 C THR K 78 24.987 −2.67426.515 1.00 0.00 C ATOM 1023 O THR K 78 25.974 −2.7 27.236 1.00 0.00 OATOM 1024 CB THR K 78 22.881 −3.339 27.78 1.00 0.00 C ATOM 1025 OG1 THRK 78 23.43 −3.473 29.094 1.00 0.00 O ATOM 1026 CG2 THR K 78 22.894 −4.7127.107 1.00 0.00 C ATOM 1035 N PRO K 63 2.314 −6.507 19.331 1.00 0.00 NATOM 1036 CA PRO K 63 3.18 −6.771 20.468 1.00 0.00 C ATOM 1038 C PRO K63 4.349 −7.725 20.289 1.00 0.00 C ATOM 1039 O PRO K 63 5.423 −7.44520.802 1.00 0.00 O ATOM 1040 CB PRO K 63 2.244 −7.213 21.576 1.00 0.00 CATOM 1043 CG PRO K 63 0.981 −6.425 21.298 1.00 0.00 C ATOM 1046 CD PRO K63 0.977 −6.194 19.795 1.00 0.00 C

TABLE 7 ATOM 1 N ILE K 5 28.121 −7.663 2.389 1.00 0.00 N ATOM 2 CA ILE K5 27.537 −8.933 2.847 1.00 0.00 C ATOM 3 C ILE K 5 26.933 −8.728 4.2401.00 0.00 C ATOM 4 O ILE K 5 25.896 −9.292 4.558 1.00 0.00 O ATOM 5 CBILE K 5 28.544 −10.118 2.780 1.00 0.00 C ATOM 6 CG1 ILE K 5 27.845−11.446 3.142 1.00 0.00 C ATOM 7 CG2 ILE K 5 29.809 −9.894 3.618 1.000.00 C ATOM 8 CD1 ILE K 5 28.630 −12.682 2.730 1.00 0.00 C ATOM 9 N ALAK 6 27.652 −7.885 5.078 1.00 0.00 N ATOM 10 CA ALA K 6 27.188 −7.5446.421 1.00 0.00 C ATOM 11 C ALA K 6 25.850 −6.821 6.317 1.00 0.00 C ATOM12 O ALA K 6 24.876 −7.223 6.940 1.00 0.00 O ATOM 13 CB ALA K 6 28.205−6.721 7.207 1.00 0.00 C ATOM 14 N ALA K 7 25.842 −5.715 5.472 1.00 0.00N ATOM 15 CA ALA K 7 24.627 −4.946 5.207 1.00 0.00 C ATOM 16 C ALA K 723.504 −5.870 4.742 1.00 0.00 C ATOM 17 O ALA K 7 22.387 −5.777 5.2341.00 0.00 O ATOM 18 CB ALA K 7 24.850 −3.832 4.187 1.00 0.00 C ATOM 19 NGLY K 8 23.861 −6.771 3.743 1.00 0.00 N ATOM 20 CA GLY K 8 22.942 −7.7333.159 1.00 0.00 C ATOM 21 C GLY K 8 22.190 −8.547 4.197 1.00 0.00 C ATOM22 O GLY K 8 20.981 −8.701 4.105 1.00 0.00 O ATOM 23 N ALA K 9 22.983−9.120 5.181 1.00 0.00 N ATOM 24 CA ALA K 9 22.435 −9.985 6.224 1.000.00 C ATOM 25 C ALA K 9 21.368 −9.263 7.040 1.00 0.00 C ATOM 26 O ALA K9 20.289 −9.802 7.254 1.00 0.00 O ATOM 27 CB ALA K 9 23.515 −10.5577.140 1.00 0.00 C ATOM 28 N LEU K 10 21.734 −8.017 7.538 1.00 0.00 NATOM 29 CA LEU K 10 20.857 −7.260 8.435 1.00 0.00 C ATOM 30 C LEU K 1019.538 −6.964 7.722 1.00 0.00 C ATOM 31 O LEU K 10 18.472 −7.283 8.2351.00 0.00 O ATOM 32 CB LEU K 10 21.475 −5.951 8.973 1.00 0.00 C ATOM 33CG LEU K 10 22.328 −6.133 10.246 1.00 0.00 C ATOM 34 CD1 LEU K 10 23.675−6.796 9.973 1.00 0.00 C ATOM 35 CD2 LEU K 10 22.563 −4.777 10.912 1.000.00 C ATOM 36 N ILE K 11 19.650 −6.281 6.514 1.00 0.00 N ATOM 37 CA ILEK 11 18.467 −5.824 5.777 1.00 0.00 C ATOM 38 C ILE K 11 17.578 −7.0055.372 1.00 0.00 C ATOM 39 O ILE K 11 16.360 −6.901 5.425 1.00 0.00 OATOM 40 CB ILE K 11 18.795 −4.856 4.606 1.00 0.00 C ATOM 41 CG1 ILE K 1117.524 −4.109 4.147 1.00 0.00 C ATOM 42 CG2 ILE K 11 19.480 −5.544 3.4211.00 0.00 C ATOM 43 CD1 ILE K 11 17.822 −2.876 3.306 1.00 0.00 C ATOM 44N GLY K 12 18.241 −8.146 4.933 1.00 0.00 N ATOM 45 CA GLY K 12 17.555−9.364 4.535 1.00 0.00 C ATOM 46 C GLY K 12 16.642 −9.865 5.635 1.000.00 C ATOM 47 O GLY K 12 15.472 −10.131 5.399 1.00 0.00 O ATOM 48 N GLYK 13 17.246 −10.004 6.877 1.00 0.00 N ATOM 49 CA GLY K 13 16.527 −10.4638.054 1.00 0.00 C ATOM 50 C GLY K 13 15.268 −9.650 8.300 1.00 0.00 CATOM 51 O GLY K 13 14.189 −10.202 8.473 1.00 0.00 O ATOM 52 N GLY K 1415.468 −8.276 8.332 1.00 0.00 N ATOM 53 CA GLY K 14 14.388 −7.324 8.5441.00 0.00 C ATOM 54 C GLY K 14 13.234 −7.535 7.579 1.00 0.00 C ATOM 55 OGLY K 14 12.086 −7.620 7.992 1.00 0.00 O ATOM 56 N LEU K 15 13.605−7.585 6.240 1.00 0.00 N ATOM 57 CA LEU K 15 12.661 −7.745 5.129 1.000.00 C ATOM 58 C LEU K 15 11.777 −8.963 5.401 1.00 0.00 C ATOM 59 O LEUK 15 10.558 −8.853 5.398 1.00 0.00 O ATOM 60 CB LEU K 15 13.400 −7.8243.771 1.00 0.00 C ATOM 61 CG LEU K 15 12.529 −7.641 2.510 1.00 0.00 CATOM 62 CD1 LEU K 15 13.428 −7.309 1.318 1.00 0.00 C ATOM 63 CD2 LEU K15 11.700 −8.879 2.169 1.00 0.00 C ATOM 64 N ILE K 16 12.463 −10.1535.628 1.00 0.00 N ATOM 65 CA ILE K 16 11.799 −11.454 5.776 1.00 0.00 CATOM 66 C ILE K 16 10.735 −11.338 6.868 1.00 0.00 C ATOM 67 O ILE K 169.582 −11.680 6.643 1.00 0.00 O ATOM 68 CB ILE K 16 12.803 −12.619 6.0391.00 0.00 C ATOM 69 CG1 ILE K 16 13.659 −12.895 4.782 1.00 0.00 C ATOM70 CG2 ILE K 16 12.086 −13.909 6.458 1.00 0.00 C ATOM 71 CD1 ILE K 1614.930 −13.674 5.089 1.00 0.00 C ATOM 72 N MET K 17 11.186 −10.883 8.1011.00 0.00 N ATOM 73 CA MET K 17 10.325 −10.873 9.285 1.00 0.00 C ATOM 74C MET K 17 9.112 −9.969 9.083 1.00 0.00 C ATOM 75 O MET K 17 7.992−10.376 9.358 1.00 0.00 O ATOM 76 CB MET K 17 11.072 −10.480 10.569 1.000.00 C ATOM 77 CG MET K 17 11.965 −11.617 11.063 1.00 0.00 C ATOM 78 SDMET K 17 12.781 −11.152 12.622 1.00 0.00 S ATOM 79 CE MET K 17 14.229−10.299 11.947 1.00 0.00 C ATOM 80 N ALA K 18 9.381 −8.681 8.641 1.000.00 N ATOM 81 CA ALA K 18 8.335 −7.661 8.530 1.00 0.00 C ATOM 82 C ALAK 18 7.251 −8.073 7.536 1.00 0.00 C ATOM 83 O ALA K 18 6.066 −7.9787.829 1.00 0.00 O ATOM 84 CB ALA K 18 8.898 −6.297 8.153 1.00 0.00 CATOM 85 N GLY K 19 7.717 −8.515 6.304 1.00 0.00 N ATOM 86 CA GLY K 196.829 −9.005 5.260 1.00 0.00 C ATOM 87 C GLY K 19 5.987 −10.160 5.7671.00 0.00 C ATOM 88 O GLY K 19 4.781 −10.204 5.565 1.00 0.00 O ATOM 89 NGLY K 20 6.707 −11.134 6.437 1.00 0.00 N ATOM 90 CA GLY K 20 6.099−12.302 7.039 1.00 0.00 C ATOM 91 C GLY K 20 4.913 −11.965 7.916 1.000.00 C ATOM 92 O GLY K 20 3.864 −12.584 7.803 1.00 0.00 O ATOM 93 N ALAK 21 5.151 −10.963 8.844 1.00 0.00 N ATOM 94 CA ALA K 21 4.174 −10.5659.849 1.00 0.00 C ATOM 95 C ALA K 21 2.837 −10.204 9.219 1.00 0.00 CATOM 96 O ALA K 21 1.807 −10.745 9.602 1.00 0.00 O ATOM 97 CB ALA K 214.669 −9.411 10.713 1.00 0.00 C ATOM 98 N ILE K 22 2.887 −9.210 8.2461.00 0.00 N ATOM 99 CA ILE K 22 1.657 −8.691 7.639 1.00 0.00 C ATOM 100C ILE K 22 0.932 −9.798 6.872 1.00 0.00 C ATOM 101 O ILE K 22 −0.288−9.878 6.917 1.00 0.00 O ATOM 102 CB ILE K 22 1.811 −7.360 6.845 1.000.00 C ATOM 103 CG1 ILE K 22 2.660 −7.427 5.557 1.00 0.00 C ATOM 104 CG2ILE K 22 2.377 −6.274 7.765 1.00 0.00 C ATOM 105 CD1 ILE K 22 1.848−7.745 4.310 1.00 0.00 C ATOM 106 N GLY K 23 1.741 −10.663 6.142 1.000.00 N ATOM 107 CA GLY K 23 1.204 −11.765 5.363 1.00 0.00 C ATOM 108 CGLY K 23 0.376 −12.709 6.211 1.00 0.00 C ATOM 109 O GLY K 23 −0.767−13.004 5.889 1.00 0.00 O ATOM 110 N ALA K 24 1.042 −13.206 7.322 1.000.00 N ATOM 111 CA ALA K 24 0.432 −14.149 8.256 1.00 0.00 C ATOM 112 CALA K 24 −0.867 −13.592 8.834 1.00 0.00 C ATOM 113 O ALA K 24 −1.841−14.320 8.961 1.00 0.00 O ATOM 114 CB ALA K 24 1.385 −14.552 9.378 1.000.00 C ATOM 115 N GLY K 25 −0.837 −12.253 9.209 1.00 0.00 N ATOM 116 CAGLY K 25 −1.989 −11.554 9.762 1.00 0.00 C ATOM 117 C GLY K 25 −3.224−11.712 8.896 1.00 0.00 C ATOM 118 O GLY K 25 −4.270 −12.142 9.367 1.000.00 O ATOM 119 N ILE K 26 −3.049 −11.314 7.575 1.00 0.00 N ATOM 120 CAILE K 26 −4.123 −11.406 6.580 1.00 0.00 C ATOM 121 C ILE K 26 −4.608−12.856 6.541 1.00 0.00 C ATOM 122 O ILE K 26 −5.800 −13.101 6.670 1.000.00 O ATOM 123 CB ILE K 26 −3.723 −10.885 5.167 1.00 0.00 C ATOM 124CG1 ILE K 26 −3.329 −9.390 5.154 1.00 0.00 C ATOM 125 CG2 ILE K 26−4.818 −11.147 4.125 1.00 0.00 C ATOM 126 CD1 ILE K 26 −4.410 −8.4235.617 1.00 0.00 C ATOM 127 N GLY K 27 −3.622 −13.815 6.331 1.00 0.00 NATOM 128 CA GLY K 27 −3.902 −15.227 6.118 1.00 0.00 C ATOM 129 C GLY K27 −4.862 −15.800 7.143 1.00 0.00 C ATOM 130 O GLY K 27 −5.885 −16.3696.784 1.00 0.00 O ATOM 131 N ASP K 28 −4.461 −15.632 8.465 1.00 0.00 NATOM 132 CA ASP K 28 −5.235 −16.133 9.607 1.00 0.00 C ATOM 133 C ASP K28 −6.691 −15.707 9.464 1.00 0.00 C ATOM 134 O ASP K 28 −7.587 −16.5419.509 1.00 0.00 O ATOM 135 CB ASP K 28 −4.707 −15.657 10.975 1.00 0.00 CATOM 136 CG ASP K 28 −3.539 −16.488 11.442 1.00 0.00 C ATOM 137 OD1 ASPK 28 −2.373 −16.308 11.122 1.00 0.00 O ATOM 138 OD2 ASP K 28 −3.957−17.506 12.234 1.00 0.00 O ATOM 139 N GLY K 29 −6.886 −14.338 9.315 1.000.00 N ATOM 140 CA GLY K 29 −8.205 −13.736 9.279 1.00 0.00 C ATOM 141 CGLY K 29 −9.036 −14.339 8.166 1.00 0.00 C ATOM 142 O GLY K 29 −10.008−15.041 8.410 1.00 0.00 O ATOM 143 N VAL K 30 −8.603 −14.009 6.889 1.000.00 N ATOM 144 CA VAL K 30 −9.444 −14.243 5.714 1.00 0.00 C ATOM 145 CVAL K 30 −9.809 −15.722 5.590 1.00 0.00 C ATOM 146 O VAL K 30 −10.974−16.055 5.423 1.00 0.00 O ATOM 147 CB VAL K 30 −8.921 −13.639 4.378 1.000.00 C ATOM 148 CG1 VAL K 30 −8.803 −12.116 4.474 1.00 0.00 C ATOM 149CG2 VAL K 30 −7.604 −14.230 3.864 1.00 0.00 C ATOM 150 N ALA K 31 −8.745−16.616 5.628 1.00 0.00 N ATOM 151 CA ALA K 31 −8.927 −18.027 5.299 1.000.00 C ATOM 152 C ALA K 31 −9.775 −18.719 6.360 1.00 0.00 C ATOM 153 OALA K 31 −10.740 −19.402 6.043 1.00 0.00 O ATOM 154 CB ALA K 31 −7.605−18.761 5.097 1.00 0.00 C ATOM 155 N GLY K 32 −9.344 −18.541 7.669 1.000.00 N ATOM 156 CA GLY K 32 −9.973 −19.223 8.786 1.00 0.00 C ATOM 157 CGLY K 32 −11.448 −18.886 8.852 1.00 0.00 C ATOM 158 O GLY K 32 −12.311−19.748 8.739 1.00 0.00 O ATOM 159 N ASN K 33 −11.697 −17.540 9.067 1.000.00 N ATOM 160 CA ASN K 33 −13.041 −17.042 9.353 1.00 0.00 C ATOM 161 CASN K 33 −14.030 −17.338 8.237 1.00 0.00 C ATOM 162 O ASN K 33 −15.195−17.586 8.518 1.00 0.00 O ATOM 163 CB ASN K 33 −13.082 −15.548 9.6821.00 0.00 C ATOM 164 CG ASN K 33 −12.429 −15.313 11.027 1.00 0.00 C ATOM165 OD1 ASN K 33 −11.228 −15.123 11.150 1.00 0.00 O ATOM 166 ND2 ASN K33 −13.304 −15.391 12.084 1.00 0.00 N ATOM 167 N ALA K 34 −13.550−17.251 6.936 1.00 0.00 N ATOM 168 CA ALA K 34 −14.421 −17.507 5.7901.00 0.00 C ATOM 169 C ALA K 34 −15.122 −18.859 5.907 1.00 0.00 C ATOM170 O ALA K 34 −16.319 −18.947 5.666 1.00 0.00 O ATOM 171 CB ALA K 34−13.694 −17.415 4.452 1.00 0.00 C ATOM 172 N LEU K 35 −14.314 −19.9446.241 1.00 0.00 N ATOM 173 CA LEU K 35 −14.846 −21.307 6.228 1.00 0.00 CATOM 174 C LEU K 35 −15.971 −21.436 7.251 1.00 0.00 C ATOM 175 O LEU K35 −17.069 −21.845 6.903 1.00 0.00 O ATOM 176 CB LEU K 35 −13.772−22.394 6.421 1.00 0.00 C ATOM 177 CG LEU K 35 14.300 −23.840 6.297 1.000.00 C ATOM 178 CD1 LEU K 35 −15.047 −24.085 4.985 1.00 0.00 C ATOM 179CD2 LEU K 35 −13.141 −24.824 6.390 1.00 0.00 C ATOM 180 N ILE K 36−15.638 −21.099 8.558 1.00 0.00 N ATOM 181 CA ILE K 36 −16.600 −21.2559.659 1.00 0.00 C ATOM 182 C ILE K 36 −17.882 −20.429 9.441 1.00 0.00 CATOM 183 O ILE K 36 −18.949 −20.824 9.886 1.00 0.00 O ATOM 184 CB ILE K36 −15.962 −21.030 11.062 1.00 0.00 C ATOM 185 CG1 ILE K 36 −16.871−21.445 12.238 1.00 0.00 C ATOM 186 CG2 ILE K 36 −15.510 −19.587 11.2731.00 0.00 C ATOM 187 CD1 ILE K 36 −17.169 −22.935 12.277 1.00 0.00 CATOM 188 N SER K 37 −17.738 −19.213 8.783 1.00 0.00 N ATOM 189 CA SER K37 −18.885 −18.361 8.470 1.00 0.00 C ATOM 190 C SER K 37 −19.842 −19.0647.503 1.00 0.00 C ATOM 191 O SER K 37 −21.048 −19.060 7.714 1.00 0.00 OATOM 192 CB SER K 37 −18.468 −16.998 7.904 1.00 0.00 C ATOM 193 OG SER K37 −17.726 −16.273 8.882 1.00 0.00 O ATOM 194 N GLY K 38 −19.250 −19.6086.368 1.00 0.00 N ATOM 195 CA GLY K 38 −20.018 −20.200 5.286 1.00 0.00 CATOM 196 C GLY K 38 −20.674 −21.495 5.719 1.00 0.00 C ATOM 197 O GLY K38 −21.892 −21.595 5.801 1.00 0.00 O ATOM 198 N VAL K 39 −19.771 −22.5245.962 1.00 0.00 N ATOM 199 CA VAL K 39 −20.202 −23.854 6.388 1.00 0.00 CATOM 200 C VAL K 39 −20.585 −23.634 7.851 1.00 0.00 C ATOM 201 O VAL K39 −19.755 −23.371 8.710 1.00 0.00 O ATOM 202 CB VAL K 39 −19.109−24.938 6.216 1.00 0.00 C ATOM 203 CG1 VAL K 39 −19.600 −26.295 6.7261.00 0.00 C ATOM 204 CG2 VAL K 39 −18.706 −25.084 4.746 1.00 0.00 C ATOM205 N ALA K 40 −21.950 −23.720 8.052 1.00 0.00 N ATOM 206 CA ALA K 40−22.661 −23.216 9.225 1.00 0.00 C ATOM 207 C ALA K 40 −24.147 −23.5119.031 1.00 0.00 C ATOM 208 O ALA K 40 −24.767 −24.137 9.880 1.00 0.00 OATOM 209 CB ALA K 40 −22.458 −21.723 9.480 1.00 0.00 C ATOM 210 N ARG K41 −24.700 −23.008 7.852 1.00 0.00 N ATOM 211 CA ARG K 41 −26.085−23.274 7.460 1.00 0.00 C ATOM 212 C ARG K 41 −26.211 −24.778 7.215 1.000.00 C ATOM 213 O ARG K 41 −27.000 −25.451 7.864 1.00 0.00 O ATOM 214 CBARG K 41 −26.570 −22.473 6.234 1.00 0.00 C ATOM 215 CG ARG K 41 −26.713−20.966 6.485 1.00 0.00 C ATOM 216 CD ARG K 41 −25.452 −20.174 6.1351.00 0.00 C ATOM 217 NE ARG K 41 −25.678 −18.741 6.386 1.00 0.00 N ATOM218 CZ ARG K 41 −25.452 −18.101 7.583 1.00 0.00 C ATOM 219 NH1 ARG K 41−25.060 −18.741 8.738 1.00 0.00 N ATOM 220 NH2 ARG K 41 −25.621 −16.7427.672 1.00 0.00 N ATOM 221 N GLN K 42 −25.370 −25.293 6.231 1.00 0.00 NATOM 222 CA GLN K 42 −25.068 −26.723 6.170 1.00 0.00 C ATOM 223 C GLN K42 −24.106 −26.908 7.346 1.00 0.00 C ATOM 224 O GLN K 42 −23.120 −26.1877.425 1.00 0.00 O ATOM 225 CB GLN K 42 −24.378 −27.132 4.861 1.00 0.00 CATOM 226 CG GLN K 42 −25.309 −26.988 3.656 1.00 0.00 C ATOM 227 CD GLN K42 −24.569 −27.351 2.387 1.00 0.00 C ATOM 228 OE1 GLN K 42 −23.890−26.535 1.781 1.00 0.00 O ATOM 229 NE2 GLN K 42 −24.697 −28.671 2.0181.00 0.00 N ATOM 230 N PRO K 43 −24.423 −27.890 8.291 1.00 0.00 N ATOM231 CA PRO K 43 −23.884 −27.878 9.642 1.00 0.00 C ATOM 232 C PRO K 43−22.377 −27.648 9.717 1.00 0.00 C ATOM 233 O PRO K 43 −21.587 −28.2649.010 1.00 0.00 O ATOM 234 CB PRO K 43 −24.244 −29.240 10.215 1.00 0.00C ATOM 235 CG PRO K 43 −25.513 −29.627 9.485 1.00 0.00 C ATOM 236 CD PROK 43 −25.436 −28.920 8.145 1.00 0.00 C ATOM 237 N GLU K 44 −22.018−26.729 10.698 1.00 0.00 N ATOM 238 CA GLU K 44 −20.630 −26.532 11.1091.00 0.00 C ATOM 239 C GLU K 44 −20.263 −27.787 11.901 1.00 0.00 C ATOM240 O GLU K 44 −20.648 −27.973 13.047 1.00 0.00 O ATOM 241 CB GLU K 44−20.357 −25.222 11.885 1.00 0.00 C ATOM 242 CG GLU K 44 −21.282 −24.89713.065 1.00 0.00 C ATOM 243 CD GLU K 44 −20.874 −23.584 13.689 1.00 0.00C ATOM 244 OE1 GLU K 44 −21.169 −22.482 13.249 1.00 0.00 O ATOM 245 OE2GLU K 44 −20.084 −23.772 14.778 1.00 0.00 O ATOM 246 N ALA K 45 −19.503−28.690 11.171 1.00 0.00 N ATOM 247 CA ALA K 45 −19.111 −29.993 11.7001.00 0.00 C ATOM 248 C ALA K 45 −17.820 −30.392 10.992 1.00 0.00 C ATOM249 O ALA K 45 −16.751 −30.343 11.586 1.00 0.00 O ATOM 250 CB ALA K 45−20.221 −31.038 11.595 1.00 0.00 C ATOM 251 N GLN K 46 −17.945 −30.7429.651 1.00 0.00 N ATOM 252 CA GLN K 46 −16.777 −31.025 8.812 1.00 0.00 CATOM 253 C GLN K 46 −15.948 −29.747 8.696 1.00 0.00 C ATOM 254 O GLN K46 −14.745 −29.762 8.923 1.00 0.00 O ATOM 255 CB GLN K 46 −17.123−31.555 7.408 1.00 0.00 C ATOM 256 CG GLN K 46 −17.621 −33.004 7.3921.00 0.00 C ATOM 257 CD GLN K 46 −19.006 −33.186 7.986 1.00 0.00 C ATOM258 OE1 GLN K 46 −19.859 −32.308 7.971 1.00 0.00 O ATOM 259 NE2 GLN K 46−19.226 −34.446 8.491 1.00 0.00 N ATOM 260 N GLY K 47 −16.657 −28.6148.311 1.00 0.00 N ATOM 261 CA GLY K 47 −16.039 −27.303 8.201 1.00 0.00 CATOM 262 C GLY K 47 −15.338 −26.879 9.479 1.00 0.00 C ATOM 263 O GLY K47 −14.240 −26.342 9.441 1.00 0.00 O ATOM 264 N ARG K 48 −16.061 −27.09010.644 1.00 0.00 N ATOM 265 CA ARG K 48 −15.555 −26.706 11.960 1.00 0.00C ATOM 266 C ARG K 48 −14.231 −27.405 12.262 1.00 0.00 C ATOM 267 O ARGK 48 −13.287 −26.756 12.689 1.00 0.00 O ATOM 268 CB ARG K 48 −16.597−26.944 13.061 1.00 0.00 C ATOM 269 CG ARG K 48 −16.186 −26.354 14.4131.00 0.00 C ATOM 270 CD ARG K 48 −17.369 −26.238 15.367 1.00 0.00 C ATOM271 NE ARG K 48 −17.915 −27.575 15.655 1.00 0.00 N ATOM 272 CZ ARG K 48−19.183 −27.822 16.126 1.00 0.00 C ATOM 273 NH1 ARG K 48 −20.102 −26.84016.422 1.00 0.00 N ATOM 274 NH2 ARG K 48 −19.592 −29.116 16.330 1.000.00 N ATOM 275 N LEU K 49 −14.204 −28.779 12.049 1.00 0.00 N ATOM 276CA LEU K 49 −13.005 −29.597 12.271 1.00 0.00 C ATOM 277 C LEU K 49−11.827 −29.081 11.437 1.00 0.00 C ATOM 278 O LEU K 49 −10.702 −29.02711.916 1.00 0.00 O ATOM 279 CB LEU K 49 −13.275 −31.090 11.982 1.00 0.00C ATOM 280 CG LEU K 49 −12.083 −32.036 12.236 1.00 0.00 C ATOM 281 CD1LEU K 49 −11.677 −32.080 13.709 1.00 0.00 C ATOM 282 CD2 LEU K 49−12.425 −33.444 11.754 1.00 0.00 C ATOM 283 N PHE K 50 −12.130 −28.75910.121 1.00 0.00 N ATOM 284 CA PHE K 50 −11.132 −28.301 9.155 1.00 0.00C ATOM 285 C PHE K 50 −10.455 −27.011 9.641 1.00 0.00 C ATOM 286 O PHE K50 −9.236 −26.909 9.608 1.00 0.00 O ATOM 287 CB PHE K 50 −11.767 −28.1167.763 1.00 0.00 C ATOM 288 CG PHE K 50 −10.777 −28.053 6.628 1.00 0.00 CATOM 289 CD1 PHE K 50 −10.020 −26.882 6.371 1.00 0.00 C ATOM 290 CE1 PHEK 50 −9.135 −26.833 5.279 1.00 0.00 C ATOM 291 CZ PHE K 50 −9.016−27.936 4.421 1.00 0.00 C ATOM 292 CE2 PHE K 50 −9.753 −29.103 4.6641.00 0.00 C ATOM 293 CD2 PHE K 50 −10.628 −29.162 5.761 1.00 0.00 C ATOM294 N THR K 51 −11.316 −25.991 10.042 1.00 0.00 N ATOM 295 CA THR K 51−10.914 −24.586 10.190 1.00 0.00 C ATOM 296 C THR K 51 −9.594 −24.38710.960 1.00 0.00 C ATOM 297 O THR K 51 −8.750 −23.638 10.482 1.00 0.00 OATOM 298 CB THR K 51 −12.056 −23.684 10.725 1.00 0.00 C ATOM 299 OG1 THRK 51 −13.156 −23.711 9.813 1.00 0.00 O ATOM 300 CG2 THR K 51 −11.641−22.223 10.839 1.00 0.00 C ATOM 301 N PRO K 52 −9.405 −25.041 12.1901.00 0.00 N ATOM 302 CA PRO K 52 −8.158 −24.960 12.932 1.00 0.00 C ATOM303 C PRO K 52 −6.858 −25.075 12.146 1.00 0.00 C ATOM 304 O PRO K 52−5.885 −24.428 12.506 1.00 0.00 O ATOM 305 CB PRO K 52 −8.261 −26.04313.991 1.00 0.00 C ATOM 306 CG PRO K 52 −9.743 −26.108 14.284 1.00 0.00C ATOM 307 CD PRO K 52 −10.411 −25.728 12.977 1.00 0.00 C ATOM 308 N PHEK 53 −6.854 −25.955 11.068 1.00 0.00 N ATOM 309 CA PHE K 53 −5.670−26.171 10.235 1.00 0.00 C ATOM 310 C PHE K 53 −5.125 −24.829 9.739 1.000.00 C ATOM 311 O PHE K 53 −3.942 −24.556 9.891 1.00 0.00 O ATOM 312 CBPHE K 53 −5.936 −27.142 9.069 1.00 0.00 C ATOM 313 CG PHE K 53 −4.673−27.523 8.331 1.00 0.00 C ATOM 314 CD1 PHE K 53 −4.287 −26.835 7.1531.00 0.00 C ATOM 315 CD2 PHE K 53 −3.860 −28.588 8.795 1.00 0.00 C ATOM316 CE1 PHE K 53 −3.117 −27.201 6.460 1.00 0.00 C ATOM 317 CE2 PHE K 53−2.693 −28.953 8.097 1.00 0.00 C ATOM 318 CZ PHE K 53 −2.322 −28.2626.930 1.00 0.00 C ATOM 319 N PHE K 54 −6.042 −23.989 9.109 1.00 0.00 NATOM 320 CA PHE K 54 −5.632 −22.714 8.512 1.00 0.00 C ATOM 321 C PHE K54 −4.879 −21.890 9.557 1.00 0.00 C ATOM 322 O PHE K 54 −3.748 −21.4769.337 1.00 0.00 O ATOM 323 CB PHE K 54 −6.794 −21.857 7.962 1.00 0.00 CATOM 324 CG PHE K 54 −7.478 −22.388 6.726 1.00 0.00 C ATOM 325 CD1 PHE K54 −6.776 −22.516 5.501 1.00 0.00 C ATOM 326 CD2 PHE K 54 −8.868 −22.6676.744 1.00 0.00 C ATOM 327 CE1 PHE K 54 −7.453 −22.895 4.325 1.00 0.00 CATOM 328 CE2 PHE K 54 −9.540 −23.037 5.565 1.00 0.00 C ATOM 329 CZ PHE K54 −8.835 −23.146 4.354 1.00 0.00 C ATOM 330 N ILE K 55 −5.602 −21.61610.711 1.00 0.00 N ATOM 331 CA ILE K 55 −5.139 −20.632 11.690 1.00 0.00C ATOM 332 C ILE K 55 −3.881 −21.077 12.435 1.00 0.00 C ATOM 333 O ILE K55 −3.018 −20.252 12.706 1.00 0.00 O ATOM 334 CB ILE K 55 −6.240 −20.10912.653 1.00 0.00 C ATOM 335 CG1 ILE K 55 −6.944 −21.221 13.459 1.00 0.00C ATOM 336 CG2 ILE K 55 −7.249 −19.271 11.863 1.00 0.00 C ATOM 337 CD1ILE K 55 −7.916 −20.694 14.499 1.00 0.00 C ATOM 338 N THR K 56 −3.815−22.415 12.811 1.00 0.00 N ATOM 339 CA THR K 56 −2.675 −22.938 13.5611.00 0.00 C ATOM 340 C THR K 56 −1.407 −22.838 12.711 1.00 0.00 C ATOM341 O THR K 56 −0.371 −22.417 13.208 1.00 0.00 O ATOM 342 CB THR K 56−2.921 −24.337 14.185 1.00 0.00 C ATOM 343 OG1 THR K 56 −1.991 −24.55015.248 1.00 0.00 O ATOM 344 CG2 THR K 56 −2.789 −25.522 13.234 1.00 0.00C ATOM 345 N VAL K 57 −1.512 −23.258 11.387 1.00 0.00 N ATOM 346 CA VALK 57 −0.372 −23.191 10.471 1.00 0.00 C ATOM 347 C VAL K 57 0.068 −21.73210.327 1.00 0.00 C ATOM 348 O VAL K 57 1.259 −21.469 10.285 1.00 0.00 OATOM 349 CB VAL K 57 −0.628 −23.887 9.109 1.00 0.00 C ATOM 350 CG1 VAL K57 0.515 −23.659 8.115 1.00 0.00 C ATOM 351 CG2 VAL K 57 −0.791 −25.3999.300 1.00 0.00 C ATOM 352 N GLY K 58 −0.931 −20.773 10.232 1.00 0.00 NATOM 353 CA GLY K 58 −0.646 −19.343 10.177 1.00 0.00 C ATOM 354 C GLY K58 0.245 −18.856 11.314 1.00 0.00 C ATOM 355 O GLY K 58 1.223 −18.15411.094 1.00 0.00 O ATOM 356 N LEU K 59 −0.170 −19.229 12.585 1.00 0.00 NATOM 357 CA LEU K 59 0.563 −18.847 13.797 1.00 0.00 C ATOM 358 C LEU K59 1.995 −19.390 13.755 1.00 0.00 C ATOM 359 O LEU K 59 2.950 −18.68014.037 1.00 0.00 O ATOM 360 CB LEU K 59 −0.175 −19.306 15.071 1.00 0.00C ATOM 361 CG LEU K 59 0.460 −18.836 16.396 1.00 0.00 C ATOM 362 CD1 LEUK 59 0.454 −17.314 16.532 1.00 0.00 C ATOM 363 CD2 LEU K 59 −0.280−19.457 17.578 1.00 0.00 C ATOM 364 N VAL K 60 2.103 −20.735 13.437 1.000.00 N ATOM 365 CA VAL K 60 3.383 −21.445 13.401 1.00 0.00 C ATOM 366 CVAL K 60 4.304 −20.826 12.329 1.00 0.00 C ATOM 367 O VAL K 60 5.497−20.677 12.556 1.00 0.00 O ATOM 368 CB VAL K 60 3.168 −22.974 13.2431.00 0.00 C ATOM 369 CG1 VAL K 60 4.467 −23.717 12.973 1.00 0.00 C ATOM370 CG2 VAL K 60 2.530 −23.575 14.502 1.00 0.00 C ATOM 371 N GLU K 613.707 −20.485 11.121 1.00 0.00 N ATOM 372 CA GLU K 61 4.409 −19.82810.011 1.00 0.00 C ATOM 373 C GLU K 61 5.144 −18.585 10.515 1.00 0.00 CATOM 374 O GLU K 61 6.304 −18.381 10.182 1.00 0.00 O ATOM 375 CB GLU K61 3.458 −19.496 8.840 1.00 0.00 C ATOM 376 CG GLU K 61 4.128 −18.6957.725 1.00 0.00 C ATOM 377 CD GLU K 61 3.185 −18.379 6.589 1.00 0.00 CATOM 378 OE1 GLU K 61 1.978 −18.211 6.690 1.00 0.00 O ATOM 379 OE2 GLU K61 3.875 −18.199 5.434 1.00 0.00 O ATOM 380 N ALA K 62 4.398 −17.72311.310 1.00 0.00 N ATOM 381 CA ALA K 62 4.961 −16.490 11.858 1.00 0.00 CATOM 382 C ALA K 62 6.272 −16.759 12.595 1.00 0.00 C ATOM 383 O ALA K 627.268 −16.086 12.362 1.00 0.00 O ATOM 384 CB ALA K 62 3.985 −15.75512.765 1.00 0.00 C ATOM 385 N ALA K 63 6.222 −17.786 13.532 1.00 0.00 NATOM 386 CA ALA K 63 7.397 −18.184 14.304 1.00 0.00 C ATOM 387 C ALA K63 8.559 −18.562 13.385 1.00 0.00 C ATOM 388 O ALA K 63 9.683 −18.13913.615 1.00 0.00 O ATOM 389 CB ALA K 63 7.109 −19.317 15.286 1.00 0.00 CATOM 390 N TYR K 64 8.256 −19.413 12.328 1.00 0.00 N ATOM 391 CA TYR K64 9.285 −19.912 11.410 1.00 0.00 C ATOM 392 C TYR K 64 10.073 −18.79610.731 1.00 0.00 C ATOM 393 O TYR K 64 11.269 −18.949 10.526 1.00 0.00 OATOM 394 CB TYR K 64 8.751 −20.857 10.318 1.00 0.00 C ATOM 395 CG TYR K64 8.211 −22.195 10.773 1.00 0.00 C ATOM 396 CD1 TYR K 64 8.685 −22.86811.933 1.00 0.00 C ATOM 397 CD2 TYR K 64 7.247 −22.847 9.964 1.00 0.00 CATOM 398 CE1 TYR K 64 8.206 −24.146 12.270 1.00 0.00 C ATOM 399 CE2 TYRK 64 6.796 −24.141 10.271 1.00 0.00 C ATOM 400 CZ TYR K 64 7.279 −24.78411.431 1.00 0.00 C ATOM 401 OH TYR K 64 6.844 −26.049 11.786 1.00 0.00 OATOM 402 N PHE K 65 9.364 −17.669 10.325 1.00 0.00 N ATOM 403 CA PHE K65 10.059 −16.531 9.710 1.00 0.00 C ATOM 404 C PHE K 65 11.164 −16.01510.631 1.00 0.00 C ATOM 405 O PHE K 65 12.265 −15.736 10.172 1.00 0.00 OATOM 406 CB PHE K 65 9.145 −15.353 9.328 1.00 0.00 C ATOM 407 CG PHE K65 8.256 −15.625 8.140 1.00 0.00 C ATOM 408 CD1 PHE K 65 6.850 −15.5588.269 1.00 0.00 C ATOM 409 CE1 PHE K 65 6.019 −15.722 7.147 1.00 0.00 CATOM 410 CZ PHE K 65 6.578 −15.970 5.883 1.00 0.00 C ATOM 411 CE2 PHE K65 7.973 −16.052 5.738 1.00 0.00 C ATOM 412 CD2 PHE K 65 8.808 −15.8776.858 1.00 0.00 C ATOM 413 N ILE K 66 10.810 −15.851 11.967 1.00 0.00 NATOM 414 CA ILE K 66 11.764 −15.375 12.973 1.00 0.00 C ATOM 415 C ILE K66 12.951 −16.337 13.006 1.00 0.00 C ATOM 416 O ILE K 66 14.086 −15.89312.915 1.00 0.00 O ATOM 417 CB ILE K 66 11.140 −15.149 14.379 1.00 0.00C ATOM 418 CG1 ILE K 66 10.099 −14.011 14.323 1.00 0.00 C ATOM 419 CG2ILE K 66 12.227 −14.831 15.415 1.00 0.00 C ATOM 420 CD1 ILE K 66 9.228−13.930 15.564 1.00 0.00 C ATOM 421 N ASN K 67 12.652 −17.685 13.1801.00 0.00 N ATOM 422 CA ASN K 67 13.703 −18.702 13.320 1.00 0.00 C ATOM423 C ASN K 67 14.701 −18.596 12.170 1.00 0.00 C ATOM 424 O ASN K 6715.900 −18.535 12.401 1.00 0.00 O ATOM 425 CB ASN K 67 13.186 −20.15113.395 1.00 0.00 C ATOM 426 CG ASN K 67 12.499 −20.446 14.713 1.00 0.00C ATOM 427 OD1 ASN K 67 11.286 −20.373 14.846 1.00 0.00 O ATOM 428 ND2ASN K 67 13.361 −20.767 15.738 1.00 0.00 N ATOM 429 N LEU K 68 14.148−18.617 10.895 1.00 0.00 N ATOM 430 CA LEU K 68 14.952 −18.648 9.6721.00 0.00 C ATOM 431 C LEU K 68 15.897 −17.447 9.657 1.00 0.00 C ATOM432 O LEU K 68 17.102 −17.606 9.507 1.00 0.00 O ATOM 433 CB LEU K 6814.060 −18.741 8.415 1.00 0.00 C ATOM 434 CG LEU K 68 14.812 −19.0627.106 1.00 0.00 C ATOM 435 CD1 LEU K 68 13.884 −19.801 6.142 1.00 0.00 CATOM 436 CD2 LEU K 68 15.348 −17.806 6.416 1.00 0.00 C ATOM 437 N ALA K69 15.280 −16.209 9.799 1.00 0.00 N ATOM 438 CA ALA K 69 16.020 −14.9509.727 1.00 0.00 C ATOM 439 C ALA K 69 17.139 −14.903 10.766 1.00 0.00 CATOM 440 O ALA K 69 18.266 −14.546 10.449 1.00 0.00 O ATOM 441 CB ALA K69 15.107 −13.737 9.887 1.00 0.00 C ATOM 442 N PHE K 70 16.758 −15.24312.059 1.00 0.00 N ATOM 443 CA PHE K 70 17.670 −15.188 13.199 1.00 0.00C ATOM 444 C PHE K 70 18.884 −16.072 12.927 1.00 0.00 C ATOM 445 O PHE K70 20.011 −15.631 13.104 1.00 0.00 O ATOM 446 CB PHE K 70 16.975 −15.56814.523 1.00 0.00 C ATOM 447 CG PHE K 70 17.885 −15.411 15.718 1.00 0.00C ATOM 448 CD1 PHE K 70 18.073 −14.141 16.317 1.00 0.00 C ATOM 449 CE1PHE K 70 18.941 −13.990 17.415 1.00 0.00 C ATOM 450 CZ PHE K 70 19.631−15.104 17.928 1.00 0.00 C ATOM 451 CE2 PHE K 70 19.449 −16.372 17.3461.00 0.00 C ATOM 452 CD2 PHE K 70 18.578 −16.527 16.251 1.00 0.00 C ATOM453 N MET K 71 18.608 −17.374 12.522 1.00 0.00 N ATOM 454 CA MET K 7119.663 −18.364 12.302 1.00 0.00 C ATOM 455 C MET K 71 20.669 −17.82011.295 1.00 0.00 C ATOM 456 O MET K 71 21.861 −17.837 11.565 1.00 0.00 OATOM 457 CB MET K 71 19.144 −19.738 11.845 1.00 0.00 C ATOM 458 CG MET K71 18.539 −20.532 13.001 1.00 0.00 C ATOM 459 SD MET K 71 17.840 −22.08912.369 1.00 0.00 S ATOM 460 CE MET K 71 17.151 −22.720 13.919 1.00 0.00C ATOM 461 N ALA K 72 20.140 −17.350 10.096 1.00 0.00 N ATOM 462 CA ALAK 72 20.987 −16.868 9.002 1.00 0.00 C ATOM 463 C ALA K 72 21.948 −15.7789.479 1.00 0.00 C ATOM 464 O ALA K 72 23.143 −15.836 9.214 1.00 0.00 OATOM 465 CB ALA K 72 20.171 −16.371 7.810 1.00 0.00 C ATOM 466 N LEU K73 21.352 −14.740 10.188 1.00 0.00 N ATOM 467 CA LEU K 73 22.105 −13.60310.723 1.00 0.00 C ATOM 468 C LEU K 73 23.219 −14.134 11.625 1.00 0.00 CATOM 469 O LEU K 73 24.380 −13.793 11.445 1.00 0.00 O ATOM 470 CB LEU K73 21.168 −12.597 11.435 1.00 0.00 C ATOM 471 CG LEU K 73 21.770 −11.26811.940 1.00 0.00 C ATOM 472 CD1 LEU K 73 22.598 −11.416 13.216 1.00 0.00C ATOM 473 CD2 LEU K 73 22.551 −10.518 10.865 1.00 0.00 C ATOM 474 N PHEK 74 22.798 −14.976 12.647 1.00 0.00 N ATOM 475 CA PHE K 74 23.673−15.420 13.728 1.00 0.00 C ATOM 476 C PHE K 74 24.905 −16.131 13.1681.00 0.00 C ATOM 477 O PHE K 74 26.020 −15.816 13.560 1.00 0.00 O ATOM478 CB PHE K 74 22.924 −16.299 14.751 1.00 0.00 C ATOM 479 CG PHE K 7423.732 −16.543 16.002 1.00 0.00 C ATOM 480 CD1 PHE K 74 24.581 −17.67216.106 1.00 0.00 C ATOM 481 CE1 PHE K 74 25.344 −17.887 17.269 1.00 0.00C ATOM 482 CZ PHE K 74 25.264 −16.982 18.342 1.00 0.00 C ATOM 483 CE2PHE K 74 24.421 −15.860 18.254 1.00 0.00 C ATOM 484 CD2 PHE K 74 23.658−15.640 17.091 1.00 0.00 C ATOM 485 N VAL K 75 24.559 −17.162 12.2651.00 0.00 N ATOM 486 CA VAL K 75 25.740 −18.022 11.768 1.00 0.00 C ATOM487 C VAL K 75 26.806 −17.217 11.023 1.00 0.00 C ATOM 488 O VAL K 7527.988 −17.509 11.151 1.00 0.00 O ATOM 489 CB VAL K 75 25.296 −19.27010.961 1.00 0.00 C ATOM 490 CG1 VAL K 75 24.498 −20.225 11.849 1.00 0.00C ATOM 491 CG2 VAL K 75 24.524 −18.965 9.677 1.00 0.00 C ATOM 492 N PHEK 76 26.338 −16.197 10.199 1.00 0.00 N ATOM 493 CA PHE K 76 27.254−15.284 9.518 1.00 0.00 C ATOM 494 C PHE K 76 28.106 −14.562 10.570 1.000.00 C ATOM 495 O PHE K 76 29.327 −14.567 10.485 1.00 0.00 O ATOM 496 CBPHE K 76 26.514 −14.307 8.577 1.00 0.00 C ATOM 497 CG PHE K 76 27.428−13.236 8.034 1.00 0.00 C ATOM 498 CD1 PHE K 76 27.372 −11.920 8.5571.00 0.00 C ATOM 499 CD2 PHE K 76 28.398 −13.540 7.048 1.00 0.00 C ATOM500 CE1 PHE K 76 28.293 −10.945 8.136 1.00 0.00 C ATOM 501 CE2 PHE K 7629.317 −12.561 6.628 1.00 0.00 C ATOM 502 CZ PHE K 76 29.271 −11.2687.180 1.00 0.00 C ATOM 503 N ALA K 77 27.390 −13.889 11.554 1.00 0.00 NATOM 504 CA ALA K 77 28.022 −12.981 12.509 1.00 0.00 C ATOM 505 C ALA K77 29.158 −13.664 13.265 1.00 0.00 C ATOM 506 O ALA K 77 30.255 −13.12613.348 1.00 0.00 O ATOM 507 CB ALA K 77 27.020 −12.372 13.488 1.00 0.00C ATOM 508 N THR K 78 28.833 −14.872 13.873 1.00 0.00 N ATOM 509 CA THRK 78 29.831 −15.665 14.586 1.00 0.00 C ATOM 510 C THR K 78 30.768−16.240 13.544 1.00 0.00 C ATOM 511 O THR K 78 31.932 −16.523 13.7911.00 0.00 O ATOM 512 CB THR K 78 29.211 −16.756 15.490 1.00 0.00 C ATOM513 OG1 THR K 78 30.185 −17.218 16.432 1.00 0.00 O ATOM 514 CG2 THR K 7828.636 −17.966 14.756 1.00 0.00 C

1. A binding site in the Fo part of an ATPase characterised in that itcomprises the resistance-conferring mutation sites of an atpE protein.2. A binding site according to claim 1 wherein the resistance-conferringmutation sites refer to amino acids 14 to 34 and to amino acids 53 to 69of an atpe protein, taking the numbering of Mtb_S (SEQ ID No.1) or ofMtb_R (SEQ ID No.2) as a reference.
 3. A binding site according to claim1 comprising at least the amino acids Ala²⁴, Gly²⁷, Phe⁵³, Val⁵⁷, Gly⁵⁸,Glu⁶¹, Tyr⁶⁴ and Phe⁶⁵ of one C subunit and the amino acids Ser¹⁸²,Leu¹⁸³, Leu¹⁸⁵ Arg¹⁸⁶ of one A subunit.
 4. A binding site according toclaim 4 wherein said amino acids have the atomic coordinates of any ofTables 3, 4 or 5 or homologous structure coordinates comprising a rootmean square deviation of non-hydrogen atoms of less than about 1.5 Å. 5.Use of a binding site according to claim 1 in a method to identifycompounds that interact with the F₀ part of an ATPase and to theirpotential as anti-microbial compounds.
 6. A method to evaluate thepotential of a test compound to interact with an atpE protein, saidmethod comprising: a) molecular modeling techniques to generate thethree-dimensional structure of a binding site according to claim 1; bemploying computational means to perform a fitting operation between thetest compound and the three-dimensional structure of the binding site;and c) analyzing the results of said fitting operation to quantify theassociation of the test compound with the three-dimensional structure ofthe binding site.
 7. A method according to claim 6 wherein the threedimensional structure is generated with at least the amino acids Ala²⁴,Gly²⁷, Phe⁵³, Val⁵⁷, Gly⁵⁸, Glu⁶¹, Tyr⁶⁴ and Phe⁶⁵ of one C subunit andthe amino acids Ser¹⁸², Leu¹⁸³, Leu¹⁸⁵, and Arg¹⁸⁶ of one A subunit,using the atomic coordinates of any of Tables 3, 4 or 5 or homologousstructure coordinates comprising a root mean square deviation ofnon-hydrogen atoms of less than about 1.5 Å.
 8. A method according toclaim 6 wherein the three-dimensional structure is generated using theatomic coordinates of the amino acids Ala²¹, Gly²⁵ of the A Chain of anyof Tables 3, 4 or 5; the amino acids Ala²⁴, Gly²⁷, Phe⁵³, Phe⁵⁴, Val⁵⁷,Gly⁵¹, Glu⁶¹, Tyr⁶⁴, Phe⁶⁵ of the K Chain of any of Tables 3, 4 or 5;the amino acids Met¹⁷, Gly¹⁹, Gly²⁰, Ala²¹, Ile²² Gly²³, Ala²⁴ Gly²⁵,Ile²⁶, Gly²⁷, Asp²⁸, Gly²⁹, Ala³¹, Phe⁵³, Thr⁵⁶, Val⁵⁷, Gly⁵⁸, Leu⁵⁹,Val⁶⁰, Glu⁶¹, Ala⁶², Ala⁶³/Pro⁶³, Tyr⁶⁴, Phe⁶⁵ of the L Chain of any ofTables 3, 4 or 5; and of the amino acids Ser¹⁸², Leu¹¹³, Leu¹¹⁵, andArg¹¹⁶ of the M Chain of any of Tables 3, 4 or
 5. 9. A method oftreating a subject with a microbially-based infection, comprisingadministering to the subject a compound that interacts with an atpEprotein at the resistance-conferring mutation sites.
 10. A methodaccording to claim 9, wherein the resistance-conferring mutation sitesrefer to amino acids 14 to 34 and to amino acids 53 to 69 of an atpEprotein, taking the numbering of Mtb_S (SEQ ID No.1) or of Mtb_R (SEQ IDNo.2) as a reference.
 11. A method of treating a subject with amicrobially-based infection, comprising administering to the subject acompound that interacts with the binding site according to claim
 1. 12.Use of compounds identified using any of the aforementioned screeningmethods in a method of treating a subject with a microbially-basedinfection.
 13. Use according to claim 12 to treat infections caused byGram-positive bacteria, more particular mycobacteria, and mostparticular against infections caused by M. africanum, M. avium, M.bovis, M. bovis-BCG, M. chelonae, M. fortuitum, M. gordonae, M.intracellulare, M. kansasii, M. microti, M. scrofulaceum, M.paratuberculosis, M. leprea, M. tuberculosis, M. ulcerans and M. ranae.14. Use according to claim 12 to treat central nervous systeminfections, external ear infections, infections of the middle ear, suchas acute otitis media, infections of the cranial sinuses, eyeinfections, infections of the oral cavity, such as infections of theteeth, gums and mucosa, upper respiratory tract infections, lowerrespiratory tract infections, genitourinary infections, gastrointestinalinfections, gynecological infections, septicemia, bone and jointinfections, skin and skin structure infections, bacterial endocarditis,burns, antibacterial prophylaxis of surgery, and antibacterialprophylaxis in immunosuppressed patients, such as patients receivingcancer chemotherapy, or organ transplant patients.
 15. Use of DARQ J inthe manufacture of a medicament for treating a bacterial infectionprovided that said infection is other than a mycobacterial infection.16. An isolated mutant atpE protein wherein the mutation consists of atleast one point mutation located in any one of amino acids 20 to 40, inparticular 30 to 40 or of amino acids 60 to 75, in particular 62 to 73as shown in the sequence alignment of FIG.
 2. 17. An isolated mutantatpE protein according to claim 16 wherein the mutation consists of atleast one point mutation, in amino acid 34 or amino acid 69 as shown inthe sequence alignment of FIG.
 2. 18. An isolated mutant atpE proteinaccording to claim 17, selected from Mtb_R (SEQ ID No.2), Msm_R09 (SEQID No.4), Msm_R10 (SEQ ID No.5) and an amino acid sequence having atleast 70, 80, 90, 95, 97 or 98% sequence identity to Mtb_R, Msm_R09 orMsm_R10.
 19. An isolated nucleic acid sequence encoding an isolatedmutant atpE protein according to claim
 16. 20. A vector comprising thenucleic acid sequence according to claim
 19. 21. A host cell carryingthe vector according to claim
 20. 22. A method for identifying ananti-microbial compound, said method comprising: a) contacting cellsexpressing an atpE protein with a test compound under physiologicalconditions, and b) determining whether the test compound interacts withthe atpE protein.
 23. A method according to claim 22, wherein the atpEprotein is selected from the group consisting of: a) SwissProt entryQ10598 or a protein having at least 70, 80, 90, 95, 97 or 98% sequenceidentity to SwissProt entry Q10598; and b) a mutant atpE proteinaccording to claim
 1. 24. A method to identify whether a test compoundbinds to an isolated atpE protein, said method comprising: a) contactingcells expressing an atpE protein wherein such cells do not normallyexpress said atpE protein, with the test compound in the presence andabsence of a compound known to bind the atpE protein, b) determine thebinding of the test compound to the atpE protein using the compoundknown to bind to the atpE protein as a reference.
 25. A method accordingto claim 24 wherein the atpE protein is selected from the groupconsisting of: a) SwissProt entry Q10598 or a protein having at least70, 80, 90, 95, 97 or 98% sequence identity to SwissProt entry Q10598;and b) a mutant atpE protein according to any one of claims 16 to 18.26. A method according to claim 24, wherein the compound known to bindto the atpE protein is detectably labeled, and consists of (J).
 27. Amethod according to claim 24 wherein step a) consists of contacting acellular composition comprising an atpE protein, with the test compoundin the presence and absence of a compound known to bind the atpEprotein.
 28. A method to identify whether a test compound binds to anisolated atpE protein, said method comprising: a) contacting cellsexpressing an atpE protein wherein such cells do not normally expresssaid atpE protein, with the test compound in the presence and absence ofa compound known to bind the atpE protein, b) determine the binding ofthe test compound to the atpE protein using the compound known to bindto the atpE protein as a reference, wherein step a) consists ofcontacting a cellular composition comprising an atpE protein, with thetest compound in the presence and absence of a compound known to bindthe atpE protein, wherein the cellular composition consists of amembrane preparation obtained from a host cell comprising an isolatednucleic acid encoding an isolated mutant atpE protein wherein themutation consists of at least one point mutation located in any one ofamino acids 20 to 40, in particular 30 to 40 or of amino acids 60 to 75,in particular 62 to 73 as shown in the sequence alignment of FIG.
 2. 29.A method for evaluating the potential of a test compound to interactwith an atpE protein, said method comprising: a) using molecularmodeling techniques to formulate a three-dimensional structure of theatpE protein: b) employing computational means to perform a fittingoperation between the test compound and the three-dimensional structureof the atpE protein: and c) analyzing the results of said fittingoperation to quantify the association of the test compound with thethree-dimensional structure of the atpE protein.
 30. A method accordingto claim 29 wherein the three-dimensional structure of the atpE proteinis generated using the atomic coordinates of the Ile28, Glu61 and Ile63of E. coli (Protein Database 1Q01) +/− a root mean square deviation ofthe backbone atoms of said amino acids of not more that 10 Å.
 31. Amethod according to claim 29 wherein the three-dimensional structure ofthe atpE protein is generated using the atomic coordinates according totables 6 or 7+/− a root mean square deviation of the backbone atoms ofsaid amino acids of not more that 1.5 Å.